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PubMed1998

The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster.

The Drosophila Polycomb group (PcG) of genes is required for the epigenetic regulation of a number of important developmental genes, including the homeotic (Hox) genes. The members of this gene family encode proteins that do not share sequence similarity, implying that each plays a unique role in this epigenetic repression mechanism. Polycomblike (Pcl) was the second PcG gene to be identified. We report here the isolation and characterization of a human cDNA, termed PHF1, which encodes a protein with significant sequence similarity to Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL includes the two PHD fingers (C4-H-C3 motif), the region between them, and sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this 258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ hybridization. While several genetic diseases that are likely to result from developmental abnormalities map to this region, PHF1 is not a clear candidate gene for any of them.

Amino Acid Sequence↗
PubMed1997

Gene expression and development databases for C. elegans

The nematode worm C. elegans, with its transparent body, is an excellent vehicle for studying developmental gene expression during embryogenesis and throughout its short life. Expression data from in-situ hybridization, immunolocalization and reporter constructs have been put into the ACeDB database, which is used to store and disseminate most types of C. elegans data, and is also widely used for genome-sequencing projects. In the database, the gene-expression patterns are linked to genes, sequences, cells, organs and the developmental stage in which expression occurs. An accessory program 'Angler' can be used to browse sectional Nomarski images of the worm embryo during early development, and to relate these images to overlaid cell lineage data and 3-D schematic views of cell positions.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗
PubMed2001

Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.

Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functional characteristics, HFL22w was studied by generating expressed sequence tags (ESTs) and by analyzing the compiled expression profiles of liver at different developmental stages. A total of 13,077 ESTs were sequenced from a 3'-directed cDNA library of HFL22w, and classified as follows: 5819 (44.5%) matched to known genes; 5460 (41.8%) exhibited no significant homology to known genes; and the remaining 1798 (13.7%) were genomic sequences of unknown function, mitochondrial genomic sequences, or repetitive sequences. Integration of ESTs of known human genes generated a profile including 1660 genes that could be divided into 15 gene categories according to their functions. Genes related to general housekeeping, ESTs associated with hematopoiesis, and liver-specific genes were highly expressed. Genes for signal transduction and those associated with diseases, abnormalities, or transcription regulation were also noticeably active. By comparing the expression profiles, we identified six gene groups that were associated with different developmental stages of human fetal liver, tumorigenesis, different physiological functions of Itoh cells against the other types of hepatic cells, and fetal hematopoiesis. The gene expression profile therefore reflected the unique functional characteristics of HFL22w remarkably. Meanwhile, 110 full-length cDNAs of novel genes were cloned and sequenced. These novel genes might contribute to our understanding of the unique functional characteristics of the human fetal liver at 22 wk.

Cloning, Molecular↗
PubMed1994

Redundant functions of the genes knirps and knirps-related for the establishment of anterior Drosophila head structures.

Developmental gene functions of Drosophila are typically characterized by a recognizable mutant phenotype. When molecular probes of such genes were used to isolate homologues, distinct spatially and temporally restricted expression patterns were observed in vertebrates as well. However, corresponding "gene knock-outs" often revealed subtle or no scorable phenotypes, a phenomenon attributed to redundant gene functions. We found that the evolutionarily related genes knirps (kni) and knirps-related (knrl) contribute to a similar phenomenon in Drosophila. The two closely situated genes show identical expression patterns in the developing embryo, including the posterior and anterior expression domains in the blastoderm. Here we show that the two biochemically equivalent gene products are both functional in the head anlage and that the lack of one gene activity can be overcome by the activity of the other. Whereas kni is also required for abdominal segmentation, knrl is nonfunctional in its posterior expression domain. Thus, the kni/knrl pair of genes provides a region-specific buffering system, rather than a case of global functional redundancy.

Animals↗
PubMed2005

Preaxial polydactyly: a model for defective long-range regulation in congenital abnormalities.

Point mutations in the long-range, limb-specific regulatory element of the SHH gene are responsible for the human limb abnormality called preaxial polydactyly (PPD). Disruptions of regulatory elements in developmental genes are a small but increasingly significant class of mutations responsible for congenital defects. Identifying regulatory elements that might reside hundreds of kilobases from their relevant genes is difficult but rendered possible by the emerging field of comparative genomics. Genetic analysis of PPD highlights the notion that regulatory mutations might generate phenotypes distinct from any of those identified for coding region mutations.

Animals↗
PubMed2003

Macro effects of microRNAs in plants.

MicroRNAs (miRNAs) are 20- to 22-nucleotide fragments that regulate expression of mRNAs that have complementary sequences. They are numerous and widespread among eukaryotes, being conserved throughout evolution. The few miRNAs that have been fully characterized were found in Caenorhabditis elegans and are required for development. Recently, a study of miRNAs isolated from Arabidopsis showed that here also developmental genes are putative regulatory targets. A role for miRNAs have in plant development is supported by the developmental phenotypes of mutations in the genes required for miRNA processing.

Gene Expression Regulation, Plant↗
PubMed2002

Developmental evolution: Hox proteins ring the changes.

The evolution of body form is believed to involve changes in expression of developmental genes, largely through changes in cis-regulatory elements. Recent studies suggest that changes in the sequences of key developmental regulators, such as the Hox proteins, may also play an important role.

Animals↗
PubMed2004

Target genes of the developmental regulator PRIB of the mushroom Lentinula edodes.

Using the method of genomic binding-site cloning, we identified three target genes of the developmental regulator, the product of priB gene (PRIB) in Lentinula edodes: the previously cloned priB and uck1 (UMP-CMP kinase gene) and a new gene, which we named mfbC. Identification of the former two genes was expected, because the promoter regions of priB and the gene encoding UMP-CMP kinase (uck1) have been shown to contain four or two consensus-like sequences of PRIB binding respectively. The mfbC gene contained two consensus-like sequences of PRIB binding in its promoter region and the PRIB protein bound them. The deduced 330 amino acid sequence of the product of mfbC gene (MFBC) was highly homologous to the 325 amino acid sequence of S. cerevisiae YJR070C/Lia1, the protein interacting with a putative translation initiation factor. Only the mature fruiting body of L. edodes was shown to contain the transcript of the mfbC gene almost exclusively, suggesting that mfbC may play a role in the final stage of fruiting-body formation.

Base Sequence↗
PubMed2024

DNA methylation reprogramming in teleosts.

Early embryonic development is crucially important but also remarkably diverse among animal taxa. Axis formation and cell lineage specification occur due to both spatial and temporal control of gene expression. This complex system involves various signaling pathways and developmental genes such as transcription factors as well as other molecular interactants that maintain cellular states, including several types of epigenetic marks. 5mC DNA methylation, the chemical modification of cytosines in eukaryotes, represents one such mark. By influencing the compaction of chromatin (a high-order DNA structure), DNA methylation can either repress or induce transcriptional activity. Mammals exhibit a reprogramming of DNA methylation from the parental genomes in the zygote following fertilization, and later in primordial germ cells (PGCs). Whether these periods of methylation reprogramming are evolutionarily conserved, or an innovation in mammals, is an emerging question. Looking into these processes in other vertebrate lineages is thus important, and teleost fish, with their extensive species richness, phenotypic diversity, and multiple rounds of whole genome duplication, provide the perfect research playground for answering such a question. This review aims to present a concise state of the art of DNA methylation reprogramming in early development in fish by summarizing findings from different research groups investigating methylation reprogramming patterns in teleosts, while keeping in mind the ramifications of the methodology used, then comparing those patterns to reprogramming patterns in mammals.

Animals↗
PubMed1988

Visualizing gene expression in time and space in the filamentous bacterium Streptomyces coelicolor.

Streptomycetes are prokaryotic microorganisms that exhibit a complex, mycelial fungus-like cycle of morphological differentiation. Development involves at least two spatially separated types of cells: the branching hyphae of the substrate mycelium, which penetrate the stratum upon which the colony feeds, and the upwardly protruding hyphae of the aerial mycelium, which undergo metamorphosis into spores. The luciferase-encoding luxA and luxB operon of the luminescent marine bacterium Vibrio harveyi was used as a promoter probe to visualize gene expression in differentiating colonies of Streptomyces coelicolor. Promoters for developmental genes of several kinds gave distinctive temporal and spatial patterns of light emission.

DNA, Bacterial↗
PubMed1985

Differential expression of protein S genes during Myxococcus xanthus development.

Protein S, the most abundant protein synthesized during development of the fruiting bacterium Myxococcus xanthus, is coded by two highly homologous genes called protein S gene 1 (ops) and protein S gene 2 (tps). The expression of these genes was studied with fusions of the protein S genes to the lacZ gene of Escherichia coli. The gene fusions were constructed so that expression of beta-galactosidase activity was dependent on protein S gene regulatory sequences. Both the gene 1-lacZ fusion and the gene 2-lacZ fusion were expressed exclusively during fruiting body formation (development) in M. xanthus. However, distinct patterns of induction of fusion protein activity were observed for the two genes. Gene 2 fusion activity was detected early during development on an agar surface and could also be observed during nutritional downshift in dispersed liquid culture. Gene 1 fusion activity was not detected until much later in development and was not observed after downshift in liquid culture. The time of induction of gene 1 fusion activity was correlated with the onset of sporulation, and most of the activity was spore associated. This gene fusion was expressed during glycerol-induced sporulation when gene 2 fusion activity could not be detected. The protein S genes appear to be members of distinct regulatory classes of developmental genes in M. xanthus.

Bacterial Proteins↗
PubMed1993

Syndactylies and polydactylies: embryological overview and suggested classification.

In 1978, Temtamy and McKusick classified isolated, non-syndromic polydactyly and syndactyly, using a logical anatomical approach, into five distinct types for each group. Since then, there have been considerable advances in the molecular embryology of the developing limb bud. These include the proposal that retinoic acid and/or related retinoids are the morphogens responsible for the morphogenetic gradient giving rise to anterior-posterior pattern formation of the limb bud, the suggestion that the HOX4 complex and other homeotic genes may also be involved in patterning, and a greater understanding of other mechanisms such as programmed cell death in the shaping of the final hand and foot. This paper briefly reviews the molecular embryology of limb development and outlines the 'end-organ responsiveness' of the limbs to a variety of single-gene mutations. An alternative classification of syndactylies and polydactylies is suggested. It is still too early to match specific defects to individual genes with precision, and it is obvious that many important developmental genes remain to be identified; nevertheless, it is envisaged that clues from molecular embryological studies will become increasingly more useful.

Animals↗
PubMed1988

Developmental regulation of two 5S ribosomal RNA genes.

The developmental regulation of two kinds of Xenopus 5S RNA genes (oocyte and somatic types) can be explained by differences in the stability of protein-protein and protein-DNA interactions in a transcription complex that directs transcription initiation by RNA polymerase III. Dissociation of transcription factors from oocyte 5S RNA genes during development allows them to be repressed by chromatin assembly. In the same cells, somatic 5S RNA genes remain active because their transcription complexes are stable.

Animals↗
PubMed1994

Distinct phenotypes generated by overexpression and suppression of S-adenosyl-L-methionine synthetase reveal developmental patterns of gene silencing in tobacco.

S-Adenosyl-L-methionine synthetase (SAM-S) catalyzes the conversion of L-methionine and ATP into S-adenosyl-L-methionine. Tobacco plants that were transformed with a construct allowing high transcription levels of an Arabidopsis sam-s gene could be grouped into two main classes based on their morphology. One class developed yellow-green leaves and had high SAM-S activity and transgene mRNA levels, whereas the other class was stunted and had leather-like leaves, very low SAM-S activity, and suppressed mRNA level of the transgene. Because both overexpression and silencing of transgene expression led to distinct, abnormal phenotypes, the developmental pattern of transgene silencing was visualized. In the lower leaves, the suppressed phenotype was associated with the veins. In successive leaves, the area of the suppressed tissue increased until all newly developed leaves displayed the suppressed phenotype. In this study, a hypothesis is presented for this developmental gene silencing. Furthermore, transgenic plants with suppressed SAM-S activity had a characteristic smell, a consequence of the accumulation of L-methionine that is converted into the volatile methanethiol.

Amino Acids↗
PubMed2006

Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth.

Among multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs), CaMKI has been shown to comprise a family of four structurally related isoforms (alpha, beta, gamma, and delta) encoded by separate genes with abundant expression in mature brain. In this study, we first examined the developmental gene expression of the four isoforms of CaMKI in mouse brain with special attention to the hippocampal formation by in situ hybridization analysis. The four isoforms of CaMKI were found to exhibit distinct spatiotemporal expression during neuronal development. We also examined the functional involvement of CaMKI in the dendritic formation of cultured hippocampal neurons. The overexpression of kinase-dead mutants of CaMKI reduced the average dendritic length of the transfected neurons without any significant effects on the number of primary dendrites and the branching index. Our present findings provide the detailed anatomical information on the developmental expression of the four isoforms of CaMKI in mouse brain, which represents the possible functional involvement of CaMKI in the basal dendritic growth of hippocampal neurons.

Animals↗
PubMed2005

Negative regulation of nuclear divisions in Caenorhabditis elegans by retinoblastoma and RNA interference-related genes.

Short RNA regulatory molecules, microRNAs, and short interfering RNAs participate in a range of developmental gene networks by base-pairing with their target sequences. Consistent with these findings, genes required for the biogenesis and function of short interfering RNAs and microRNAs, dicer (dcr-1 in Caenorhabditis elegans) and argonaute homologs, are essential for development in diverse organisms, including C. elegans. We demonstrate that genes required for the function of short RNAs synergize with the retinoblastoma tumor suppressor homolog lin-35 in negative regulation of the nuclear divisions in the intestine of C. elegans. The level of cyclin E (cye-1) expression is critical for nuclear divisions in the intestine and is elevated in double mutants in lin-35 and RNA interference pathway genes. We propose that RNA interference-related pathways cooperate with retinoblastoma in transcriptional repression of endogenous genes, an example being cyclin E.

Animals↗
PubMed2004

Adaptive evolution of HoxA-11 and HoxA-13 at the origin of the uterus in mammals.

The evolution of morphological characters is mediated by the evolution of developmental genes. Evolutionary changes can either affect cis-regulatory elements, leading to differences in their temporal and spatial regulation, or affect the coding region. Although there is ample evidence for the importance of cis-regulatory evolution, it has only recently been shown that transcription factors do not remain functionally equivalent during evolution. These results suggest that the evolution of transcription factors may play an active role in the evolution of development. To test this idea we investigated the molecular evolution of two genes essential for the development and function of the mammalian female reproductive organs, HoxA-11 and HoxA-13. We predicted that if coding-region evolution plays an active role in developmental evolution, then these genes should have experienced adaptive evolution at the origin of the mammalian female reproductive system. We report the sequences of HoxA-11 from basal mammalian and amniote taxa and analyse HoxA-11 and HoxA-13 for signatures of adaptive molecular evolution. The data demonstrate that these genes were under strong positive (directional) selection in the stem lineage of therian and eutherian mammals, coincident with the evolution of the uterus and vagina. These results support the idea that adaptive evolution of transcription factors can be an integral part in the evolution of novel structures.

Adaptation, Biological↗
PubMed1999

Epigenetic inheritance of active chromatin after removal of the main transactivator.

The Drosophila Polycomb and trithorax group proteins act through chromosomal elements such as Fab-7 to maintain repressed or active gene expression, respectively. A Fab-7 element is switched from a silenced to a mitotically heritable active state by an embryonic pulse of transcription. Here, histone H4 hyperacetylation was found to be associated with Fab-7 after activation, suggesting that H4 hyperacetylation may be a heritable epigenetic tag of the activated element. Activated Fab-7 enables transcription of a gene even after withdrawal of the primary transcription factor. This feature may allow epigenetic maintenance of active states of developmental genes after decay of their early embryonic regulators.

Acetylation↗