Testis-specific transcriptional regulators selectively occupy BORIS-bound CTCF target regions in mouse male germ cells.
Testis-specific transcriptional regulators selectively occupy BORIS-bound CTCF target regions in mouse male germ cells.
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DOI：
10.1038/srep41279
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发表时间：
2017-02-01
影响因子：
4.6
通讯作者：
Zentner GE
中科院分区：
文献类型：
--
作者：
Rivero-Hinojosa S;Kang S;Lobanenkov VV;Zentner GE
尽管在体外和体内具有相同的序列特异性，但CCCTC结合因子（CTCF）及其同源兄弟印记位点调节因子（BORIS）在生殖细胞中同时表达。最近，ChIP-seq分析揭示了两类CTCF/BORIS结合区域：在生殖细胞和BORIS阳性体细胞癌细胞中，由单独的CTCF（仅CTCF）结合的单CTCF靶位点（1xCTS）或由CTCF和BORIS（CTCF&BORIS）或单独的BORIS（仅BORIS）同时结合的双CTCF靶位点（2xCTS）。BORIS结合区（CTCF和BORIS和BORIS仅位点）相对于CTCF仅位点平均富集成熟精子中的RNA聚合酶II（RNAPII）结合和组蛋白保留，但对它们知之甚少。我们发现，CTCF和BORIS和BORIS-唯一的网站的子集被几个睾丸特异性转录调节因子（TSTR）占据，并与高表达的生殖细胞特异性基因和组蛋白保留在成熟精子。我们还证明了BORIS和分析的TSTR之一，TATA结合蛋白（TBP）相关因子7样（TAF 7 L）之间的物理相互作用。我们的数据表明，CTCF和BORIS与额外的TSTR合作，以调节发育中的雄性配子和成熟精子中的组蛋白保留的基因表达，潜在地引发基因组的某些区域在受精后快速激活。
Despite sharing the same sequence specificity in vitro and in vivo, CCCTC-binding factor (CTCF) and its paralog brother of the regulator of imprinted sites (BORIS) are simultaneously expressed in germ cells. Recently, ChIP-seq analysis revealed two classes of CTCF/BORIS-bound regions: single CTCF target sites (1xCTSes) that are bound by CTCF alone (CTCF-only) or double CTCF target sites (2xCTSes) simultaneously bound by CTCF and BORIS (CTCF&BORIS) or BORIS alone (BORIS-only) in germ cells and in BORIS-positive somatic cancer cells. BORIS-bound regions (CTCF&BORIS and BORIS-only sites) are, on average, enriched for RNA polymerase II (RNAPII) binding and histone retention in mature spermatozoa relative to CTCF-only sites, but little else is known about them. We show that subsets of CTCF&BORIS and BORIS-only sites are occupied by several testis-specific transcriptional regulators (TSTRs) and associated with highly expressed germ cell-specific genes and histone retention in mature spermatozoa. We also demonstrate a physical interaction between BORIS and one of the analyzed TSTRs, TATA-binding protein (TBP)-associated factor 7-like (TAF7L). Our data suggest that CTCF and BORIS cooperate with additional TSTRs to regulate gene expression in developing male gametes and histone retention in mature spermatozoa, potentially priming certain regions of the genome for rapid activation following fertilization.