Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Sci Rep. 2017 Feb 1;7:41279. doi: 10.1038/srep41279.
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.
尽管在体外和体内具有相同的序列特异性，但结合蛋白（CTCF）及其同源物印记调控因子（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：单 CTCF 靶位点（1xCTSes），仅由 CTCF 结合（CTCF-only）或双 CTCF 靶位点（2xCTSes）同时由 CTCF 和 BORIS 结合（CTCF&BORIS）或仅由 BORIS 结合（BORIS-only）在生殖细胞和 BORIS 阳性的体癌细胞中。与仅由 CTCF 结合的位点（CTCF-only 位点）相比，BORIS 结合的区域（CTCF&BORIS 和 BORIS-only 位点）在成熟精子中平均富含 RNA 聚合酶 II（RNAPII）结合和组蛋白保留，但对其知之甚少。我们表明，CTCF&BORIS 和 BORIS-only 位点的亚群被几个睾丸特异性转录调节剂（TSTRs）占据，并与高度表达的生殖细胞特异性基因和成熟精子中的组蛋白保留相关。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（TAF7L）之间存在物理相互作用。我们的数据表明，CTCF 和 BORIS 与其他 TSTR 合作，调节雄性配子发育过程中的基因表达和成熟精子中的组蛋白保留，可能为受精后某些基因组区域的快速激活做好准备。
