Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Helix-Loop-Helix Motifs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system.

NeuroD/BETA2, a basic helix-loop-helix transcription factor, has been shown to play a role in tissue-specific differentiation of pancreatic and enteroendocrine cells. To gain further insight into the function of neuroD/BETA2 in the nervous system development, we examined the expression pattern of neuroD/BETA2 during embryonic and postnatal development by using in situ hybridization. Dynamic changes of neuroD/BETA2 expression in the central nervous system were observed during embryogenesis, especially in telencephalon, hippocampus, cerebellum, spinal cord, and olfactory epithelium. Moderate level of expression was also detected in developing pancreas in early embryogenesis. Although the neuroD/BETA2 expression in cerebellum and hippocampus increased over time, expression in cerebral cortex, spinal cord, as well as in fetal pancreas gradually decreased as embryogenesis proceeded. High level of the neuroD/BETA2 expression in developing cerebellum and hippocampus persisted throughout postnatal development and remained at a stable level in the adult brain. Interestingly, neuroD/BETA2 expression was detected not only in postmitotic but also in mitotic cells, as was evident in its expression in external granular layer of cerebellum and granule cells of the dentate gyrus during postnatal development. This observation suggests that neuroD/BETA2 may have a unique role in proliferation, differentiation, or both, of granule cells of cerebellum and dentate gyrus.

Animals↗
PubMed1999

Analysis of the Max-binding protein MNT in human medulloblastomas.

Medulloblastomas (MBs) are the most frequent malignant brain tumors in children. The molecular pathogenesis of these tumors is still poorly understood. Microsatellite and restriction-fragment-length polymorphism studies have revealed allelic loss of genetic material on the short arm of chromosome 17 in the region 17p13 in approximately 50% of MBs, suggesting the presence of a tumor-suppressor gene in this region. A candidate for this putative tumor-suppressor is the MNT gene, located at 17p13.3 and encoding a Max-interacting nuclear protein with transcriptional-repressor activity. In this study, we analyzed MNT mRNA and protein expression in 44 MB samples, including 32 primary tumors, 3 recurrent tumors and 9 MB cell lines. Allelic loss at 17p13.3 was found in 49% of informative cases. RT-PCR showed MNT mRNA expression in all cases analyzed. Endogenous Mnt protein with an apparent molecular weight of 72 to 74 kDa was detected in lysates from MB cell lines. The presence and functional integrity of Mnt in MBs were tested in electrophoretic mobility-shift assays. These experiments demonstrated that Mnt interacts with Max, and that this heterodimer binds DNA specifically, suggesting a functional bHLHZip domain of MB-derived Mnt. In support, single-strand conformation-polymorphism (SSCP) analyses revealed no mutation in the bHLHZip region. Deletion of the Mnt Sin3 interaction domain was shown to convert Mnt from an inhibitor of myc/ras-co-transformation into a molecule capable of cooperating with Ras in transformation. This region therefore was screened for mutation by SSCP: again, no alterations were found. These findings indicate that the MNT gene located at 17p13.3 is not likely to be involved in the molecular pathogenesis of MBs.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1997

Helix bending as a factor in protein/DNA recognition.

Normal vectors perpendicular to individual base pairs are a powerful tool for studying the bending behavior of B-DNA, both in the form of normal vector plots and in matrices that list angles between vectors for all possible base pair combinations. A new analysis program, FREEHELIX, has been written for this purpose, and applied to 86 examples of sequence-specific protein/DNA complexes whose coordinates are on deposit in the Nucleic Acid Data Base. Bends in this sample of 86 structures almost invariably follow from roll angles between adjacent base pairs; tilt makes no net contribution. Roll in a direction compressing the broad major groove is much more common than that which compresses the minor groove. Three distinct types of B-DNA bending are observed, each with a different molecular origin: (1) Localized kinking is produced by large roll at single steps or at two steps separated by one turn of helix. (2) Smooth, planar curvature is produced by positive and negative roll angles spaced a half-turn apart, with random side-to-side zigzag roll at intermediate points, rather than a tilt contribution that might have been expected theoretically. (3) Three-dimensional writhe results from significant roll angles at a continuous series of steps. Writhe need not change the overall direction of helix axis, if it is continued indefinitely or for an integral number of helical turns. A-DNA itself can be formally considered as possessing uniform, continuous writhe that yields no net helix bending. Smooth curvature is the most intricate deformation of the three, and is least common. Writhe is the simplest deformation and is most common; indeed, a low level of continuous writhe is the normal condition of an otherwise unbent B-DNA helix of general sequence. With one exception, every example of major kinking in this sample of 86 structures involves a pyrimidine-purine step: C-A/T-G, T-A, or C-G. Purine-purine steps, especially A-A, show the least tendency toward roll deformations.

Animals↗
PubMed1997

Relax, a novel rat bHLH transcriptional regulator transiently expressed in the ventricular proliferating zone of the developing central nervous system.

A number of basic helix-loop-helix containing proteins have been shown to be required for neural development at different sites or times. Here, Relax, a novel rat basic helix-loop-helix transcriptional regulator, has been isolated and characterized. Analysis of the temporal and spatial distributions shows that the Relax transcripts are detected exclusively in the central nervous system, in discrete regions from embryonic day 11.5 to 18.5. Most strikingly, Relax is expressed along two major boundaries that define the longitudinal axis in the spinal cord and the hindbrain and is a marker of the anterior tip of this axis in the forebrain. Relax-expressing cells are strictly localized in the ventricular zone of the neural tube, where neural progenitors originate. This unique pattern of expression suggests that Relax is involved in neural fate determination.

Animals↗
PubMed1997

Helix-loop-helix proteins in Schwann cells: a study of regulation and subcellular localization of Ids, REB, and E12/47 during embryonic and postnatal development.

Although basic helix-loop-helix (bHLH) proteins play an important role in transcriptional control in many cell types, the role of HLH proteins in Schwann cells has yet to be assessed. In this study, we have analyzed the expression of the dominant negative HLH genes, Id1 to Id4 and the class A gene REB, during Schwann cell development. We found that mRNA derived from these genes was present in the Schwann cell lineage throughout development including embryonic precursors and mature cells. The mRNA levels were not significantly regulated during development. Nevertheless, by using antibodies against the four different Id proteins, we found clear regulation of some of these genes at the protein level, in particular Id 2, 4, and REB, both in amount and nuclear/cytoplasmic localization. All these proteins are found in the nuclei of Schwann cell precursors but are not seen in nuclei of Schwann cells of newborn nerves. We observed extensive overlap in Id expression, especially in Schwann cell precursors that co-expressed all four Id proteins and REB. We also showed that Id 1 and 2 were up-regulated as Schwann cells progressed through the cell cycle. These data indicate that HLH transcription factors act as regulators of Schwann cell development and point to the existence of as yet unidentified cell type-specific bHLH proteins in these cells.

Aging↗
PubMed1999

Regulation of hippocampal neuronal differentiation by the basic helix-loop-helix transcription factors HES-1 and MASH-1.

HES-1 is a vertebrate homologue of the Drosophila basic helix-loop-helix (bHLH) protein Hairy, a transcriptional repressor that negatively regulates neuronal differentiation. HES-1 expression in neuronal precursors precedes and represses the expression of the neuronal commitment gene MASH-1, a bHLH activator homologous to the proneural Achaete-Scute genes in Drosophila. Down-regulation of HES-1 expression in developing neuroblasts may be necessary for the induction of a regulatory cascade of bHLH activator proteins that controls the commitment and progression of neuronal differentiation. Here we show that the differentiation of embryonic day-17 rat hippocampal neurons in culture was coincident with a decline in HES-1 expression and DNA binding. Therefore, we examined the effect of forced expression of HES-1 and MASH-1 upon nerve growth factor (NGF) -induced differentiation in TrkA transfected hippocampal neurons. Expression of HES-1 inhibited both the intrinsic and NGF-induced neurite outgrowth, whereas MASH-1 expression increased neurite outgrowth. Strikingly, the increased hippocampal differentiation observed with MASH-1 expression is completely blocked by coexpression of HES-1. Furthermore, both wild-type HES-1 and a non-DNA binding mutant of HES-1 repressed MASH-1-dependent transcription activation. These results suggest that down-regulation of HES-1 is necessary for autonomous, growth factor-induced and MASH-1-activated hippocampal differentiation.

Animals↗
PubMed1996

Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors.

The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.

Animals↗
PubMed1996

E2F1 inhibition of transcription activation by myogenic basic helix-loop-helix regulators.

Cellular transcription factor E2F1 is thought to regulate the expression of genes important for cell cycle progression and cell proliferation. Deregulated E2F1 expression induces S-phase entry in quiescent cells and inhibits myogenic differentiation. We show here that E2F1 inhibits the activation of gene transcription by myogenic basic helix-loop-helix proteins myoD and myogenin. Transfection assay using different deletion constructs indicates that both the DNA binding and the transactivation domains of E2F1 are required for its inhibition of myoD transcription activation. However, the retinoblastoma protein (RB) binding domain is not required. Furthermore, co-transfection with the RB, which inhibits the transcription activity of E2F1, can also repress E2F1 inhibition of myoD transactivation. These results suggest an essential role of E2F1-mediated transcription in its inhibition of myogenesis.

Animals↗
PubMed1998

Fibroblast growth factor downregulates expression of a basic helix-loop-helix-type transcription factor, scleraxis, in a chondrocyte-like cell line, TC6.

Scleraxis is a basic helix-loop-helix-type transcription factor that is expressed in sclerotome. Fibroblast growth factor (FGF) is one of the cytokines produced by the cells in skeletal tissues and is a potent modulator of skeletogenesis. The aim of this study was to examine the effects of FGF on the expression of scleraxis in chondrocyte-like cells, TC6. In these cells, scleraxis mRNA was constitutively expressed as a 1 .2 kb message at a high level in contrast to its low levels of expression in fibroblast-like cells or osteoblast-like cells. Upon treatment with FGF, scleraxis mRNA level was decreased within 12 h. This effect was at its nadir at 24 h and the scleraxis mRNA level returned to its base line level by 48 h. The FGF effect was maximal at 1 ng/ml. FGF effects on scleraxis were blocked by actinomycin D but not by cycloheximide, suggesting the involvement of transcriptional events that do not require new protein synthesis. The FGF effects on scleraxis were blocked by genistein, suggesting the involvement of tyrosine kinase in the post-receptor signaling. TGFbeta treatment of TC6 cells enhanced scleraxis mRNA expression; however, combination of the saturation doses of FGF and TGFbeta resulted in suppression of scleraxis mRNA level. BMP2 also suppressed scleraxis mRNA expression in TC6 cells and no further suppression was observed in combination with FGF. These results indicate that scleraxis is expressed in chondrocyte-like TC6 cells and it is one of the targets of FGF action in these cells.

Basic Helix-Loop-Helix Proteins↗
PubMed1998

Differential expression of Id genes in multipotent myeloid progenitor cells: Id-1 is induced by early-and late-acting cytokines while Id-2 is selectively induced by cytokines that drive terminal granulocytic differentiation.

Hematopoietic development is regulated by a complex mixture of cytokine growth factors that guide growth and differentiation of progenitor cell populations at different stages in their development. The genetic programs that drive this process are controlled at the molecular level by the type and number of transcriptional regulators coexpressed in the cell. Both positive- and negative-acting helix-loop-helix transcription factors are expressed during hematopoietic development, with the Id-type transdominant negative regulators controlling the net helix-loop-helix activation potential in the cell at any given time. It has been demonstrated that some of these Id factors are involved in the checkpoint at which undifferentiated progenitor cells make the commitment to terminal maturation. Therefore, we sought to determine whether these Id family factors are selectively induced or extinguished by cytokines that act at different points during hematopoiesis. NFS-60, a myeloid progenitor line that proliferates in response to multiple cytokines, was stimulated by treatment with SCF, IL-3, IL-6, G-CSF, and erythropoietin. Id-1 expression correlated tightly with cellular proliferation: it declined when growth factor stimulation was withdrawn and was quickly induced whenever the cell began to proliferate. The regulation of Id-2 was more complex: its expression was slightly upregulated in factor-deprived cells but only strongly reinduced after extended exposure to cytokines that drive granulocytic differentiation (IL-6, G-CSF, and TGFbeta). These data support a cell-cycle regulatory role for Id-1 in multipotent myeloid progenitor cells and a role for Id-2 during terminal granulocytic differentiation.

Cell Differentiation↗
PubMed1999

Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells.

Several members of the basic helix-loop-helix (bHLH) type of transcription factors have now been reported, and almost every member of this class has been implicated in transcriptional regulation in cell type determination and differentiation. Previously, we reported that dominant negative HLH proteins are involved in osteoblastic phenotype expression, such as osteocalcin, and hence differentiation (Tamura and Noda [1994] J. Cell Biol. 126:773-782). In this work, we used degenerate PCR cloning in order to identify cDNA clones encoding bHLH proteins expressed in osteoblastic osteosarcoma ROS17/2.8 cells. Sequence analyses of the 47 clones revealed that 11 clones encoded products with a characteristic motif of the bHLH transcription factor family. Of these clones, sequences in the amplified region of seven clones were homologous to the mouse twist, and three clones were homologous to the mouse twist-related HLH protein, Dermo-1. To confirm Dermo-1 mRNA expression in osteoblastic cells, we performed reverse transcription polymerase chain reaction (RT-PCR) analysis using mRNA from ROS17/2.8 cells and MC3T3-E1 cells by Dermo-1 specific primers and Northern blot analysis. These analyses demonstrated that Dermo-1 mRNA was expressed in these osteoblast-like cell lines. Nucleotide sequence analysis of the partial rat Dermo-1 cDNA cloned from ROS17/2.8 library revealed that it has the highest degree of homology with the mouse Dermo-1 cDNA, and the partial amino acid sequence deduced from the obtained rat Dermo-1 was identical with the corresponding region of the mouse Dermo-1 amino acid sequence. To further examine the role of Dermo-1 in the regulation of osteoblastic differentiation, we examined mRNA levels of Dermo-1 and twist in C3H10T1/2 cells treated with recombinant human bone morphogenetic protein (rhBMP)-2. Using the RT-PCR method, the mRNA levels of Dermo-1 and twist were found to be decreased by the treatment with rhBMP-2 in C3H10T1/2 cells. We also observed that the mRNA level of Dermo-1 was decreased about fourfold by the treatment with rhBMP-2 in C3H10T1/2 cells by Northern blot analysis. Moreover, Dermo-1 mRNA was detected at lower levels in 21-day-old differentiated MC3T3-E1 cells compared with 3-day-old undifferentiated MC3T3-E1 cells. These results suggested that Dermo-1 could be involved in the osteoblastic differentiation in a negative manner.

Amino Acid Sequence↗
PubMed1999

Remodeling of the hypertrophied human myocardium by cardiac bHLH transcription factors.

The basic helix-loop-helix transcription factors eHAND and dHAND are involved in developmental cardiac growth and differentiation. We investigated HAND gene expression in the normal and in the hypertrophied right and left ventricle of patients with tetralogy of Fallot (ToF) and hypertrophic obstructive cardiomyopathy (HOCM). HAND mRNA was constitutively expressed in the hypertrophied heart and increased in the hypertrophic tissue of both patient groups. HAND genes had a complementary left-right cardiac asymmetry of expression with dHAND predominantly in the right and eHAND in the left ventricle. The two cardiac bHLH factors have the ability to form heterodimers with the ubiquitous bHLH protein E12, subsequently recognizing E-boxes in the promoter region of target genes like ALC-1. We found a highly significant positive correlation between HAND and ALC-1 mRNA. The total ALC-1 protein level in ToF was smaller than in HOCM, although ALC-1 mRNA as well as HAND mRNA levels were significantly higher. ToF patients expressed around four times more ALC-1 mRNA for similar amounts of ALC-1 than HOCM patients. Suggesting disturbed ALC-1 translation in ToF, we found ALC-1 antisense mRNA expression in the hypertrophied, but not in the normal, ventricles. The higher the antisense/sense ALC-1 mRNA ratio, the lower ALC-1 protein was expressed.

Base Sequence↗
PubMed1999

TWIST, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage.

Basic helix-loop-helix (bHLH) transcription factors have been shown to play an important role in controlling cell type determination and differentiation. TWIST, a member of the bHLH transcription factor family, is involved in the development of mesodermally derived tissue, including the skeleton. We examined the role of human TWIST in osteoblast metabolism using stable expression of sense and antisense TWIST in human osteoblast HSaOS-2 cells. Changes in morphology and osteogenic phenotype characterized these stable clones. Cells that overexpressed TWIST exhibited a spindle shaped morphology, reduced levels of alkaline phosphatase, a reduced proliferation rate, and failed to respond to basic fibroblast growth factor (bFGF). In contrast, those that underexpressed TWIST demonstrated a cuboidal epithelial-like morphology characteristic of differentiated osteoblasts. TWIST antisense cells exhibited increased levels of alkaline phosphatase and type I collagen mRNA, initiated osteopontin mRNA expression, and had a reduced proliferation rate. These results indicate that TWIST overexpressing cells may de-differentiate and remain in an osteoprogenitor-like state, and antisense TWIST cells progress to a more differentiated mature osteoblast-like state. Therefore, the level of TWIST can influence osteogenic gene expression and may act as a master switch in initiating bone cell differentiation by regulating the osteogenic cell lineage.

Alkaline Phosphatase↗
PubMed1999

Mad1 expression in the absence of differentiation: effect of cAMP on the B-lymphoid cell line Reh.

The protein Mad1 heterodimerizes with Max to form an E-box binding complex able to interfere with the transcriptional and transforming activities of c-Myc. Downregulation of c-Myc accompanied by induction of Mad1 upon differentiation has fueled the notion that Mad1 may play a role in the cessation of proliferation associated with the differentiation process. Since studies on Mad1 expression have so far been limited to cells undergoing differentiation, it was of interest to examine Mad1 expression in a cell system unable to differentiate. To do so, we utilized the leukemia-derived B-precursor cell line, Reh, and studied the expressions of Mad1, c-Myc, Mxil, and Max during cAMP-mediated growth inhibition of these cells. Thus, the adenylate cyclase activator forskolin induced growth inhibition of the cells in the G1 phase of the cell cycle. This growth inhibition was associated with transient increased expression of Mad1 concomitant with transient downregulation of c-Myc. The Mad1 protein levels essentially paralleled those of mRNA, with peak levels at 4 h of forskolin treatment. By coimmunoprecipitation we detected increased binding of Mad1 to Max in forskolin-treated cells, indicating that the changes in Mad1 protein levels had functional implications. By continually treating Reh cells with forskolin for 72 h, we observed a sustained elevated expression of Mad1 concomitant with downregulated c-Myc expression, still without changing the differentiation profile of the Reh cells. Interestingly, we showed that other known cell cycle regulatory proteins also were transiently regulated by forskolin. To this extent, following forskolin treatment of Reh cells, cyclin E-cdk2 activity was transiently reduced concomitant with dephosphorylation of pRB. We suggest that the early changes in Mad1 and the cell cycle regulatory proteins initiate a chain of events resulting in permanent growth arrest. Thus, the increased expression of Mad1 in the absence of differentiation indicates that Mad1 expression in Reh cells is linked to growth arrest per se.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2000

Hepatocyte growth factor (HGF) inhibits skeletal muscle cell differentiation: a role for the bHLH protein twist and the cdk inhibitor p27.

Hepatocyte growth factor (HGF) plays a crucial role in regulating the differentiation of both fetal and adult skeletal myoblasts. This study aimed at defining the intracellular factors that mediate the effect of HGF on adult myoblast differentiation. HGF increased Twist expression while decreasing p27(kip1) protein levels and not affecting the induction of p21(Cip1/Waf1) in satellite cells. Like HGF, overexpression of Twist did not affect p21 expression while inhibiting muscle-specific proteins. Both ectopic Twist-antisense (Twist-AS) and p27 partially rescued the effects of HGF on bromodeoxyuridine (BrdU) incorporation and myosin heavy chain (MHC) expression in muscle satellite cells; the two plasmids together effected full rescue, suggesting that HGF independently regulates these two factors to mediate its effects. Ectopic p27 promoted differentiation in the presence of HGF by blocking the induction of Twist. Using Twist-AS to lower Twist levels restored the HGF-dependent reduction of p27 and MHC. In the presence of ectopic HGF, satellite cells formed thin mononuclear myotubes. Neither ectopic p27, Twist-AS, or their combination reversed this change in cell morphology, suggesting that HGF acts through additional mediators to inhibit downstream events during myogenesis. Taken together, the results suggest that the effects of HGF on muscle cell proliferation and differentiation are mediated through changes in the expression levels of the myogenic-inhibitory basic helix-loop-helix (bHLH) protein Twist and the cell-cycle inhibitor p27.

Animals↗
PubMed1998

Id1, Id2, and Id3 gene expression in neural cells during development.

Id1, Id2, and Id3 mRNA are expressed mainly in the proliferating ependymal cell zone of the mouse brain during embryogenesis. In this study, the expression pattern and cell phenotypes of the Id family mRNA were examined in postnatal and adult rat brain. The expression of Idl and Id3 mRNA in rat brain was observed in the cortex layer 1, corpus callosum, ventricular/subventricular zone (VZ/ SVZ), and the CA1-4 layers of the hippocampus at postnatal day 1 (P1) through P14, whereby it declined at 2 months. In general, the developmental pattern of Idl mRNA coincided with the pattern observed for Id3 mRNA. Similar to Id1 and Id3, Id2 mRNA was highly expressed in the corpus callosum, VZ/SVZ, and the hippocampus. Examination of Id2 mRNA revealed high levels in the cortex and caudate putamen at P1 through P14, whereas a decline was observed in its expression in the adult cortex. In P5 rat cerebellum, all Id mRNA examined were found in the internal granular cell layers; however, at this time point, only Id2 mRNA expression was detected in the differentiating zone of the external granular cell layers, preferentially localizing to adult Purkinje cells. Furthermore, only Id2 mRNA expression in brain was observed in NF+ neurons at P5. Examination of S100alpha+ and GFAP+ astrocytes, revealed the presence of all three mRNAs, whereas the expression of Id2 and Id3 mRNA was absent in 04+ immature oligodendrocytes. These data suggest that the spatial and temporal kinetic patterns during development, as well as cellular specificity, of the Id gene family may play a critical role in neural precursor cell proliferation and cell divergence.

Animals↗
PubMed1996

A possible role in chemical carcinogenesis for epigenetic, heritable changes in gene expression.

Although genetic changes are clearly important in the initiation of carcinogenesis, there is reason to think that epigenetic changes may also play a role in the process. A key feature of carcinogenesis is the long latency between exposure to carcinogenic insults and the appearance of malignancy. Thus, if epigenetic changes are to be involved, they must somehow be inherited at each cell division without the continued presence of the carcinogen. I propose that self-perpetuating changes in patterns of gene expression are a plausible mechanism for an epigenetic component of carcinogenesis. Networks of transcription factors that regulate each other's and their own expression are known to control important developmental processes, particularly the determination of entire cell lineages. An inherent property of many such autoregulatory networks is the existence of two very distinct, stable steady-states, defined in terms of the concentration of each transcription factor in the network. In this report, I present a model in which an acute carcinogen exposure is postulated to shift such a network from one steady-state to the other, effectively turning on or off the expression of at least one of the genes. Because of the autoregulatory nature of the network, this new steady-state is stably inherited at each cell division. Such changes in gene expression may ultimately contribute to the malignant phenotype if the regulatory network affects genes important in cell-cycle checkpoints, maintenance of genome stability, signal transduction, or other processes that are altered in tumor cells.

Animals↗
PubMed2000

Systematic identification of genes expressed during early oogenesis in medaka.

Subtractive hybridization was used to identify differences in gene expression between medaka (Oryzias latipes) males and females during sex differentiation. Fifty female-specific cDNA fragments were cloned. They can be classified into three groups by virtue of whether their earliest expression is at 1, 5, or 30 days after hatching. All 15 near full-length cDNAs belonging to the first two groups were cloned. Many of these female-specific genes are coordinately expressed in oocytes at the earliest stages of oogenesis. Some of the genes that were identified by their sequences include egg envelope proteins, oocyte-specific RNA binding proteins, and a transcription factor containing a basic helix-loop-helix motif.

Animals↗