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PubMedDate not supplied

Preservation of spermatogenesis in spinal cord injured rats with exogenous testosterone. Relationship with serum testosterone levels and cellular localization of cAMP responsive element modulator.

UNLABELLED: The current experiment examined the effects of exogenous testosterone (T) on spermatogenesis in rats with spinal cord injury (SCI) and their relationship with the cellular distribution of a cyclic AMP-responsive element modulator (CREM) in testicular cells. Implantation of T-filled Silastic capsules (TCs, 1-20 cm) resulted in dose-dependent, biphasic changes in testicular T levels and spermatogenesis in SCI rats. However, dose responsiveness of spermatogenesis to exogenous T in SCI rats differed from that in sham control rats. Specifically, implantation of 2-cm TCs enhanced the effects of SCI on spermatogenesis, resulting in total regression of the seminiferous epithelium. Although 3-cm TCs maintained complete spermatogenesis in sham control rats, this regimen failed to support complete spermatogenesis in SCI rats. Although complete spermatogenesis was maintained in SCI rats given 5-20-cm TC implants, various abnormalities persisted. Cellular distribution of CREM remained normal in SCI rats but was altered in those SCI rats that received 3- or 5-cm TC implants. Such effects were associated with reduced CREM proteins in testicular tissues. These results were consistent with altered cAMP signaling and its regulation in testicular cells after SCI and provided possible mechanistic explanations for the effects of SCI on spermatogenesis. CONCLUSION: SCI resulted in changes in the responsiveness of spermatogenesis to exogenous T. These effects were associated with altered cAMP/CREM signaling in testicular cells. Further studies, including a study of the relationship between serum T levels and normalcy of sperm functions and the role of neural-endocrine interactions in mediating the effects of SCI on spermatogenesis and sperm function, are needed so that therapeutic regimens can be designed for clinical use.

Androgens↗
PubMed2005

The cAMP pathway in combination with BMP2 regulates Phox2a transcription via cAMP response element binding sites.

Combined BMP2 and cAMP signaling induces the catechola-minergic lineage in neural crest (NC) cultures by increasing expression of the proneural transcription factor Phox2a, in a cAMP response element (CRE)-binding protein (CREB)-mediated mechanism. To determine whether CREB acts directly on Phox2a transcription induced by BMP2+cAMP-elevating agent IBMX, transient transfections of hPhox2a-reporter constructs were performed in avian NC cultures and murine, catecholaminergic CAD cells. Although BMP2+IBMX increased endogenous Phox2a expression, the 7.5-kb hPhox2a reporters expressing either luciferase or DsRed1-E5 fluorescent protein were unresponsive to BMP2+IBMX, but active in both cell types. Cell sorting of fluorescence-positive NC cells expressing the 7.5-kb hPhox2a fluorescent timer reporter differentiated to equal numbers of catecholaminergic cells as fluorescence-negative cells, suggesting inappropriate transcription from the transfected hPhox2a promoter. NC or CAD cells treated with histone deacetylase inhibitor trichostatin A and BMP2+IBMX display increased endogenous Phox2a transcription and prolonged CREB phosphorylation, indicating Phox2a chromatin remodeling is linked to CREB activation. Chromatin immunoprecipitations employing CREB, CREB-binding protein, and acetylated H4 antibodies identified two CRE half-sites at -5.5 kb in the murine Phox2a promoter, which is also conserved in the human promoter. Proximal to the CRE half-sites, within a 170-bp region, are E-box and CCAAT binding sites, also conserved in mouse and human genes. This 170-bp promoter region confers cAMP, BMP2, and enhanced BMP2+cAMP regulation to Phox2a-luciferase reporters. We conclude these CREs are functional, with CREB directly activating Phox2a transcription. Because the E-box binds bHLH proteins like ASH1 induced in NC cells by BMP2, we propose this novel 170-bp cis-acting element is a composite site, mediating the synergistic regulation by BMP2+cAMP on Phox2a transcription.

Animals↗
PubMed2006

Activation of serum response element by D2 dopamine receptor is governed by Gbetagamma-mediated MAPK and Rho pathways and regulated by RGS proteins.

In this study, we investigated the activation of the serum response element (SRE) by the D2 dopamine receptor (D2R) agonist quinpirole. Stimulation of CHO cells expressing the D2R by quinpirol evoked a dose-dependent SRE activation, which was completely blocked by overnight treatment of pertussis toxin or by co-expression of the beta-adrenergic receptor kinase C-terminus, implicating the involvement of Galpha(i )and Gbetagamma in the signal transduction. Furthermore, using MEK inhibitors and dominant negative mutants of RhoA, Rac1, and Cdc42, we showed that the Gbetagamma-mediated activation of the SRE in CHO cells utilizes both MAPK and Rho pathways. Expression of either regulator of G protein signaling 2 or 4 (RGS2 or RGS4) proteins significantly attenuated the quinpirole-induced SRE activation. These results delineate the signaling pathways which couple D2 receptor to the transcriptional activation of SRE and demonstrate a modulatory role for RGS proteins in these processes.

Animals↗
PubMed1997

Mutagenesis of a cAMP response element within the latency-associated transcript promoter of HSV-1 reduces adrenergic reactivation.

Mutagenesis of a cyclic AMP response element (CRE) within the LAT promoter of HSV-1 reduces the ability of LAT expression to be induced in transient assays, but has only a minimal impact on reactivation of the virus in in vitro systems. Here we show that a CRE mutation results in a significant reduction of adrenergically induced reactivation in vivo in the rabbit eye model. Spontaneous reactivation frequencies were also reduced. In addition, we demonstrate that this mutation has no effect on the amount of LAT expressed during latency when compared with the parent, 17syn+, and the rescuant. These results indicate a greater effect of CRE on induced reactivation in vivo than in in vitro systems, but also suggest that the CRE in the LAT promoter is not autonomous in conducting the reactivation signal.

Actins↗
PubMed2004

Enhanced binding activity of nuclear antioxidant-response element through possible formation of Nrf2/Fos-B complex after in vivo treatment with kainate in murine hippocampus.

To evaluate whether in vivo glutamate signals modulate signaling processes mediated by antioxidant-response element (ARE), we examined ARE binding in nuclear extracts from the hippocampus after in vivo treatment of mice with kainate. Enhancement of ARE binding was found at 2 h to 3 days after kainate treatment. Supershift analysis indicated possible involvement of Nrf2, Fos-B, and c-Fos in ARE binding in hippocampal nuclear extracts obtained from kainate-treated animals. On super-supershift analysis by combination of these antibodies, ARE probe/protein complex was shifted by the anti-Fos-B antibody alone, but not by the anti-c-Fos antibody alone, and further addition of the anti-Nrf2 antibody dramatically eliminated binding of the complex shifted by the anti-Fos-B antibody in hippocampal nuclear extracts from kainate-treated animals. Kainate treatment induced a profound increase in levels of c-Fos and Fos-B, without markedly affecting that of Nrf2 in nuclear extracts from the hippocampus. Co-localization of Nrf2 with both Fos-B and c-Fos was found in neuronal cell layers of the hippocampus in kainate-treated animals. RT-PCR analysis revealed that kainate treatment increases glutathione-S-transferase mRNA level in the hippocampus. Taken together, kainate signals may enhance nuclear ARE binding through an interaction between constitutive Nrf2 with inducible Fos-B expressed in murine hippocampus.

Animals↗
PubMed1998

An inverted cAMP response element mediates the cAMP induction of the ovine beta 1-adrenergic receptor gene.

We identified an inverted, functional cAMP response element (CRE) located at--1599 bp relative to the translation start site within the ovine beta 1-adrenergic receptor (beta 1 AR) gene promoter. In transfection studies with SK-N-MC cells, a 40-bp oligonucleotide containing the potential CRE, beta 1 AR-CRE, conferred a 3- to 4-fold increase in luciferase activity mediated by cAMP. The induction was mimicked by co-transfecting the cells with a vector overexpressing the alpha-catalytic subunit of the cAMP-dependent protein kinase (PKA) without treatment, and was blocked by overexpressing a PKA inhibitor (PKI). In electrophoretic mobility shift assays, a discrete binding pattern was shown in cell nuclear extract probed with the 40 bp beta 1 AR-CRE. The binding was shown to be specific and supershifted by addition of a CRE binding protein (CREB-1) antibody. These data demonstrate that cAMP mediates the induction of beta 1 AR gene expression by interacting with an inverted CRE within the promoter region. This is the first reported functional CRE among all beta 1 AR genes.

Animals↗
PubMed1998

Estrogen receptor alpha requires no accessory factors for high-affinity binding to a consensus response element.

Estrogen receptor (ER) alpha is commonly thought to bind to a consensus estrogen response element (ERE) as a homodimer, but previous experiments have not ruled out the presence of other proteins in the ERalpha/ERE complex. To characterize this interaction in more detail, we overexpressed mouse (m) ERalpha in a baculovirus system, using the selective advantage of the apoptosis inhibitor p35. Recombinant mERalpha possesses the predicted molecular weight and binds 17beta-estradiol and an oligonucleotide containing a consensus vitellogenin ERE with high affinity. Over a wide concentration range of mERalpha protein (0.1-50 nM), only one complex was detected between mERalpha and vitellogenin ERE in gel shift assays. The ratio of E2:vitellogenin ERE bound by mERalpha was close to 2:1, and each complex contained only one ERE. The molecular weight of the complex was determined to be 160 000, very close to that predicted for two mERalpha proteins and one ERE oligonucleotide, therefore providing strong evidence that no other proteins were present. Recombinant mERalpha was purified such that it was the only protein observable by silver stain. Purified mERalpha and mERalpha in a nuclear extract behaved identically in Ferguson analysis, providing more evidence that only mERalpha was binding to the ERE. Purified mERalpha bound vitellogenin ERE with high affinity (Kd = 0. 92 +/- 0.20 nM), indicating that no other proteins are necessary for high-affinity mERalpha interaction with a consensus ERE. To determine whether ERalpha in an estrogen-responsive mammalian tissue behaves the same as the overexpressed mERalpha, we tested rat uterine cytosol by Ferguson analysis. ERalpha in rat uterine cytosol behaved identically to overexpressed mERalpha, suggesting that ERalpha in the uterine extract also binds to DNA predominantly as a homodimer with no additional proteins.

Animals↗
PubMed2005

A peroxisome proliferator response elements regulatory system in xenopus oocytes and its application.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a kind of ligand-activated transcription factors binding to peroxisome proliferator response element (PPRE), a specific recognition site. It is thought to play a critical role in glucose and lipid metabolism and in inflammation control. The aim of this study was to establish a new cellular model for the quick screening of lipid-lowering drugs, which may be effective as PPAR-gamma ligands on the PPRE-mediated pathway regulatory system. METHODS: Two plasmids were constructed: pXOE-PPARgamma, in which the human PPARgamma gene was in the downstream of TFIIIA gene promoter, and pLXRN-PPRE-d2EGFP, in which the enhanced green fluorescent protein (EGFP) gene was subcloned into PPRE. The xenopus oocytes were injected with these two plasmids, and consequently treated with prostaglandin E1, pioglitazone, and different kinds of lipid-lowering drugs. After 3 days, the oocytes were observed under a fluorescence microscope. To confirm the drug action,we injected pXOE-PPARgamma plasmid into the oocytes, which then treated with prostaglandin E1 and Hawthorn flavonoids. The mass of expressed lipoprotein lipase (LPL) in the cells was determined by enzyme labeling linked immunosorbent assay (ELISA). RESULTS: The expression of EGFP was only induced by prostagalandin E1, pioglitazone, Hawthorn flavonoids. A concentration-response relationship was seen between expressed EGFP and Hawthorn flavonoids. The levels of LPL in both Hawthorn flavonoids groups and PPARgamma ligand prostagalandin E1 group injected with pXOE-PPARgamma plasmid increased significantly (< 0.001) compared with controls, and a concentration-response relationship was observed between LPL mass and Hawthorn flavonoids. CONCLUSIONS: It is possible to establish a PPRE regulatory EGFP reporter system in xenopus oocytes to monitor the activity of PPARgamma ligand. Hawthorn flavonoids can increase the expression of gene downsteam of PPRE by effect on the PPRE pathway regulatory system.

Alprostadil↗
PubMed2004

Molecular cloning of the guinea pig CYP1A2 gene 5'-flanking region: identification of functional aromatic hydrocarbon response element and characterization of CYP1A2 expression in GPC16 cells.

Aromatic hydrocarbon (AH) effects are mediated by binding of the AH receptor and its heterodimeric partner aromatic hydrocarbon nuclear translocator to specific response elements on DNA (AHREs). CYP1A2 expression is induced by AHs, yet AHREs have been identified in CYP1A2 genes of only two species and their functional role assessed only in the human gene. There have been few analyses of CYP1A2 gene regulation in nonhepatic cells. To gain further insight into CYP1A2 regulation, we cloned the initial 1.2 kilobases (kb) of the guinea pig CYP1A2 gene 5'-flanking region and characterized CYP1A2 expression in guinea pig colon adenocarcinoma cells (GPC16). Two putative AHRE sites were identified (-830 and -575 bp). They are considerably more proximal than the functional AHRE found in the human CYP1A2 gene (-2.5 kb). GPC16 cells expressed CYP1A2 after treatment with AH, enabling characterization of the putative AHRE sites in a homologous cell line. Double-stranded oligonucleotide probes, corresponding to each putative AHRE, bound in an AH-induced and specific manner to nuclear proteins prepared from GPC16 cells. In transfection analyses, only the distal site mediated AH-induced reporter gene activity. Mutation of this site suppressed AH-induced activity, supporting the concept that it is involved in AH-mediated induction of CYP1A2. However, the low level of AH-induction by the wild type suggests that other factors modulate AH-response by the CYP1A2 gene.

5' Flanking Region↗
PubMed1990

Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element.

Transcriptional regulation of the c-fos proto-oncogene requires the serum response element (SRE) which is complexed by a multi-protein assembly observed both in vitro and in vivo. Two protein factors, p67SRF and p62TCF (previously called p62), are required to interact with the SRE for efficient induction of c-fos by serum. By quantitative band shift electrophoresis we measure at least a 50-fold increase in SRE affinity for p67SRF/p62TCF over p67SRF alone. Stoichiometrically we determine that the ternary complex with p62TCF involves p67SRF in dimeric form. We demonstrate that p67SRF is a glycosylated nuclear transcription factor carrying terminal N-acetylglucosamine (GlcNAc) as a post-translational modification. A proteolytic limit digestion product, approximately 13 kd in size, was generated from the p67SRF-SRE complex. This p67SRF-core domain binds SRE, can dimerize with p67SRF and is still able to form a ternary complex with p62TCF. Therefore, three functional activities can be ascribed to this small p67SRF-core domain: specific DNA binding, dimerization and interaction with p62TCF. We demonstrate that these functions map within the p67SRF core fragment containing the region between amino acids 93 and 222.

Base Sequence↗
PubMed1992

Expression cloning of a novel zinc finger protein that binds to the c-fos serum response element.

Induction of c-fos transcription by serum growth factors requires the serum response element (SRE). The SRE is a multifunctional element which responds to several positively and negatively acting signals. To identify cellular proteins that might mediate functions of the SRE, we screened a human cDNA expression library with an SRE probe. We report the isolation and characterization of SRE-ZBP, a previously unidentified SRE-binding protein. SRE-ZBP is a member of the C2H2 zinc finger family of proteins exemplified by TFIIIA and the Drosophila Krüppel protein. The seven tandemly repeated zinc finger motifs in SRE-ZBP are sufficient for high-affinity binding to the SRE. We show that SRE-ZBP is a nuclear protein and identify a candidate cellular protein encoded by the SRE-ZBP gene. Because we cannot detect any DNA-binding activity attributable to the endogenous protein, we propose that SRE-ZBP activity may be subject to posttranslational regulation. Like c-fos mRNA, SRE-ZBP mRNA is serum inducible in HeLa cells, but with slower kinetics. The role of SRE-ZBP in the regulation of c-fos transcription remains unestablished, but this protein binds to a region of the SRE where mutations lead to derepression.

Amino Acid Sequence↗
PubMed2006

Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway.

To investigate the possibility that natural medicines affect lipid metabolism by regulating lipoprotein lipase (LPL) expression, a green fluorescent protein (GFP) gene was constructed downstream of the peroxisome proliferator response element (PPRE) and the constructed plasmid was microinjected into Xenopus oocytes to establish a PPRE regulatory reporter system. Using this system, hawthorn flavonoids were quickly selected from a panel of natural medicines and found to up-regulate GFP expression by an effect on PPRE. To confirm the effect of hawthorn flavonoids, we treated mice orally with water (control), hawthorn flavonoids, and pioglitazone and measured the LPL levels in serum, adipose tissue, and muscle by an enzyme-linked immunosorbent assay. The serum LPL levels were no different from the controls after treatment with either hawthorn flavonoids or pioglitazone, but LPL increased significantly in muscular tissues and decreased in adipose tissues. These results demonstrate that hawthorn flavonoids meditate LPL expression in mice with tissue-specific differences. A novel PPRE regulatory report system was established for rapid and effective selection and evaluation of LPL-mediating drugs.

Adipose Tissue↗
PubMed2001

The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element.

FHOS is a member of the formin homology (FH) family of proteins and is expressed at high levels in splenic cells. FH proteins link cellular signaling pathways to the actin cytoskeleton and serum response factor-dependent transcription. In these studies, the role of FHOS in Rho family GTPase signaling pathways was analyzed. FHOS interacted with the polybasic domain in the Rac1 C terminus in a guanine nucleotide-independent manner but did not interact with RhoA, Cdc42Hs, Rac2, or Rac3. Intramolecular autoinhibitory interactions between the C terminus of FHOS and an N-terminal region partially overlapping the Rac1 interaction domain were also identified. FHOS truncation mutants lacking the N- or C-terminal autoregulatory domains stimulated transcription of a c-fos serum response element (SRE)-driven reporter. Overexpression of wild-type and mutant (N17 and V12) Rac1 proteins repressed SRE induction by the N-terminal FHOS deletion mutant but not by the C-terminal FHOS deletion mutant. Immunofluorescence studies indicated that the localization of the mutant FHOS proteins might contribute to their differential responses to Rac1. Wild-type FHOS and the N-terminal deletion mutant localized to the perinuclear region and membrane edges. In contrast, the C-terminal FHOS mutants were diffusely localized. These data suggest that FHOS induces transcription from SREs by multiple pathways and that Rac1 may influence the course of some FHOS-induced signaling events.

3T3 Cells↗
PubMed1999

Analysis of cis-acting sequences and trans-acting factors regulating the interleukin-3 response element of the DUB-1 gene.

The murine DUB-1 gene is a hematopoietic-specific, immediate-early gene that encodes a growth-regulatory deubiquitinating enzyme. DUB-1 contains an IL-3-inducible enhancer element that is activated in a JAK2-dependent, STAT5-independent manner. In this study, we have further characterized this novel IL-3 response element. Transcriptional reporter assays in Ba/F3 cells revealed that two AP-1 sites, a GATA motif, and an Ets site are required for induction of DUB-1 enhancer activity. Gel shift assays indicated that IL-3 activates the binding of an AP-1 complex containing JunD to the AP-1 sites and the binding of another protein complex to the Ets motif. The latter complex was not detectable in Ba/F3 cells stably transfected with a dominant-negative mutant of JAK2. As previously shown, these cells do not express DUB-1 mRNA or protein. Furthermore, we demonstrated that GATA-1 constitutively binds to the DUB-1 enhancer element. The involvement of GATA-1 may be important for the hematopoietic-restricted expression pattern of DUB-1. This combination of inducible and constitutive elements of the DUB-1 enhancer appears to account for the unique STAT-independent expression characteristics of DUB-1.

Animals↗
PubMed2005

Identification of a novel functional androgen response element within hPar1 promoter: implications to prostate cancer progression.

Human protease-activated receptor-1 (hPar1) plays a role in malignant and physiological invasion processes. We have identified a functional androgen response element (ARE) located in the hPar1 promoter upstream of the transcription start site at -1791 to -1777. Dihydrotestosterone treatment of the prostate cancer cell line LNCaP increased endogenous hPar1 mRNA levels, consistent with the threefold increase in promoter activity of hPar1-luciferase reporter construct. Specific binding of the hPar1-derived ARE to LNCaP nuclear extracts was demonstrated by electrophoretic mobility shift assay. This binding was abrogated by antiandrogen receptor (anti-AR) antibodies or excess cold oligonucleotide but not by a mutated oligonucleotide. Moreover, using chromatin immunoprecipitation assays, we confirm the in vivo interaction between the AR and ARE domain of the hPar1 promoter. In parallel, we show that hormone ablation therapy markedly reduces the otherwise high hPar1 expression levels in prostate cancer biopsy specimens. We suggest that the hPar1 gene is regulated transcriptionally by androgens, representing one of several target genes effectively reduced during hormone ablation therapy. A major limitation of hormonal deprivation is that it causes only a temporary remission, and the cancer eventually reappears in a more malignant, androgen-independent form. hPar1 is also overexpressed in CL1 cells, an aggressively metastasizing, hormone-independent subclone of LNCaP, and in PC3 prostate adenocarcinoma lacking AR in a mechanism yet to be fully elucidated. These data may imply that hPar1 expression correlates with prostate cancer progression in androgen-dependent and -independent phases and therefore, provides an instrumental, therapeutic target for treatment in prostate cancer.

Adenocarcinoma↗
PubMed1999

Definition of a high affinity growth hormone DNA response element.

Rat liver contains a growth hormone inducible nuclear factor complex, GHINF, that binds to the growth hormone response element (GHRE) of the serine protease inhibitor (Spi) 2.1 gene. GHINF contains Stat5 and binds to paired gamma-activated sites (GAS) within the GHRE, but poorly to either one alone. By analysis of the sequence of various GAS sites that bind the GHINF complex (based on the GHRE 3' GAS motif), we demonstrate that a 13 nucleotide high affinity DNA recognition sequence (haGHRE) for GHINF complex binding is (ANTTC)C/T(N)A/G(GAA)A/T(A)/T. One copy of the haGHRE will replace the requirement for two GAS elements present in the wild type promoter in supporting a GH response in primary hepatocyte culture. Mutation of the native Spi 2.1 from a paired GAS site to a single haGHRE does not appreciably change its affinity for binding to the GHINF complex, nor does it alter its sensitivity to GH concentration.

Animals↗
PubMed1991

Identification of a novel iron-responsive element in murine and human erythroid delta-aminolevulinic acid synthase mRNA.

Iron-responsive elements (IREs) are regulatory RNA elements which are characterized by a phylogenetically defined sequence-structure motif. Their biological function is to provide a specific binding site for the IRE-binding protein (IRE-BP). Iron starvation of cells induces high affinity binding of the cytoplasmic IRE-BP to an IRE which has at least two different known biological consequences, repression of ferritin mRNA translation and stabilization of the transferrin receptor transcript. We report the identification of a novel, evolutionarily conserved IRE motif in the 5' UTR of murine and human erythroid-specific delta-aminolevulinic acid synthase (eALAS) mRNA which encodes the first, and possibly rate limiting, enzyme of the heme biosynthetic pathway. We demonstrate the function of the eALAS IRE as a specific binding site for the IRE-BP by gel retardation analyses and by in vitro translation experiments. In addition, we show that the 5' UTR of eALAS mRNA is sufficient to mediate iron-dependent translational regulation in vivo. These findings strongly suggest involvement of the IRE-IRE-BP system in the control of heme biosynthesis during erythroid differentiation.

5-Aminolevulinate Synthetase↗
PubMed1996

Analysis of binding of the 1,25-dihydroxyvitamin D3 receptor to positive and negative vitamin D response elements.

The binding of the 1,25-dihydroxyvitamin D3 receptor to the vitamin D response elements (VDREs) in the rat osteocalcin (OSC-DRE), mouse osteopontin (MOP-DRE), rat calbindin D-9k (CaBP-DRE), and human parathyroid hormone genes (PTH-DRE) was studied. Binding of VDR to the three positive VDREs is cooperative. The degree of cooperativity is highest with the calbindin VDRE compared with either the OSC-DRE or the MOP-DRE. This cooperativity is largely absent in the case of the negative element, the PTH-DRE. The VDR binds in order of decreasing affinity to PTH-DRE > OSC-DRE = MOP-DRE > CaBP-DRE. Thus, the greatest affinity is associated with the lowest degree of cooperativity. Further study has revealed that the PTH-VDRE actually consists of two repeat elements like all other VDREs and is not a single six-base sequence. A nuclear factor has also been found that binds downstream from the GGTTCA element in the PTH promoter. The binding site of this factor overlaps the PTH-DRE nucleotide sequence.

Animals↗