Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histones are essential for packaging of eukaryotic genomic DNA in nucleosomes, and histone gene expression is normally coupled with DNA synthesis. Some of the flowering plant histone genes show strictly male gamete-specific expression. However, mechanisms underlying their male gamete-specific expression have not been elucidated so far. Here we report the isolation of the male gamete-specific histone gcH3 promoter from Lilium longiflorum and its activity in the male gametic cell of the flowering plant. The OCT motif, which is well conserved in plant histone promoters regulating S phase-specific expression, is not conserved in the gcH3 promoter. Instead sequence motifs identical to GC box 1 and GC box 2, the transcriptional activator and suppressor for mammalian testis-specific histone H1t, are present in the gcH3 promoter, suggesting that plants and animals share the mechanism which governs the specificity of gene expression in male gametic cells. Male gamete-specific activation of the gcH3 promoter has been confirmed by microprojectile bombardment in lily pollen. The sperm cell carrying gold particles showed reporter gene expression, while green fluorescent protein (GFP) was absent in the other sperm cell which had no particles, confirming that the gcH3 promoter is activated in the male gametic cell, and sperm cells have transcriptional and translational machinery that is independent of the vegetative cell of pollen.
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PMID:Transcriptional activity of male gamete-specific histone gcH3 promoter in sperm cells of Lilium longiflorum. 1575 44

Aberrant hypomethylation in many cancers reactivates retrotransposons and selected single-copy genes such as cancer-testis antigens. Genes reactivated in this manner have recently been postulated to include CTCFL/BORIS, a presumptive testis-specific chromatin regulator, and OCT4/POU5F1, a transcriptional activator in pluripotent cells. We found both genes expressed at high levels in testis and at much lower levels in normal prostate tissue. In prostate and bladder carcinoma cell lines and cancer tissues expression remained largely unchanged, but individual prostate carcinomas showed modestly increased CTCFL expression compared to normal tissues. OCT4 expression was significantly decreased in cancer tissues. Promoter methylation in both genes paralleled expression levels. CTCFL, but not OCT4 was dramatically induced in cancer cell lines by 5-aza-2'-deoxycytidine, but neither gene by the histone deacetylase inhibitor suberoylanilide hydroxamic acid. Thus, CTCFL and OCT4 resemble cancer-testis antigens in being selectively hypomethylated and expressed in male germ cells but differ in lacking significant reexpression and hypomethylation in prostate carcinomas. DNA methylation appears the crucial mechanism in the control of CTCFL transcription, but less decisive in that of OCT4. These findings imply that inhibitors of DNA methylation used for cancer treatment may induce CTCFL expression. Immunohistochemistry demonstrated nuclear localization of CTCFL in developing spermatocytes, and cytoplasmatic localization in spermatogonia, Leydig cells, and epithelial prostate cells. Teratocarcinoma cell lines showed nuclear, and 5-aza-2'-deoxycytidine-treated prostate cancer lines nuclear or cytoplasmatic localization. These different localizations might indicate additional control of CTCFL function via intracellular compartmentation.
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PMID:Epigenetic control of CTCFL/BORIS and OCT4 expression in urogenital malignancies. 1685 82

Cellular differentiation and development of germ cells critically depend on a coordinated activation and repression of specific genes. The underlying regulation mechanisms, however, still lack a lot of understanding. Here, we describe that both the testis-specific transcriptional activator CREMtau (cAMP response element modulator tau) and the repressor GCNF (germ cell nuclear factor) have an overlapping binding site which alone is sufficient to direct cell type-specific expression in vivo in a heterologous promoter context. Expression of the transgene driven by the CREM/GCNF site is detectable in spermatids, but not in any somatic tissue or at any other stages during germ cell differentiation. CREMtau acts as an activator of gene transcription whereas GCNF suppresses this activity. Both factors compete for binding to the same DNA response element. Effective binding of CREM and GCNF highly depends on composition and epigenetic modification of the binding site. We also discovered that CREM and GCNF bind to each other via their DNA binding domains, indicating a complex interaction between the two factors. There are several testis-specific target genes that are regulated by CREM and GCNF in a reciprocal manner, showing a similar activation pattern as during spermatogenesis. Our data indicate that a single common binding site for CREM and GCNF is sufficient to specifically direct gene transcription in a tissue-, cell type- and differentiation-specific manner.
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PMID:Functional cooperation between CREM and GCNF directs gene expression in haploid male germ cells. 2007 44


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