Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS.
Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS.
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Gal3st1 (CST) 是精子发生所必需的基因，其睾丸特异性形式的表达受 CTCF 旁系同源基因 BORIS 的调节。
DOI：
10.1128/mcb.01093-09
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发表时间：
2010
影响因子：
5.3
通讯作者：
Lobanenkov,Victor
中科院分区：
文献类型：
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作者：
Suzuki,Teruhiko;Kosaka-Suzuki,Natsuki;Pack,Svetlana;Shin,Dong-Mi;Yoon,Jeongheon;Abdullaev,Ziedulla;Pugacheva,Elena;Morse3rd,HerbertC;Loukinov,Dmitri;Lobanenkov,Victor
以往的研究表明，CTCFs的同源基因Boris(印迹位点调节基因的兄弟)在雄性生殖细胞中表达，但其在精子发生中的作用尚未明确。为了了解Boris的功能活动，我们产生了BORIS基因敲除(KO)小鼠。纯合子为空等位基因的小鼠在精子发生方面存在缺陷，导致与细胞死亡增加相关的小睾丸。这种缺陷早在出生后第21天就很明显，表现为单倍体细胞产生延迟。通过基因表达谱分析，我们发现Gal3st1(也称为脑苷磺基转移酶[CST])的转录水平在BORISKO睾丸中显著降低，而Gal3st1在减数分裂中起着关键作用。我们发现CST在睾丸中表达为一种新的睾丸特异异构体，CST形式FTS，它有一个短的外显子1f。我们发现Boris结合并激活了CST的启动子形成FTS。启动子中Boris结合位点的突变降低了Boris激活启动子的能力。这些发现将CST表达的转录调控定义为Boris在精子发生中的关键作用。
Previously, it was shown that theCTCFparalogous gene,BORIS(brother of the regulator of imprinted sites) is expressed in male germ cells, but its function in spermatogenesis has not been defined. To develop an understanding of the functional activities of BORIS, we generatedBORISknockout (KO) mice. Mice homozygous for the null allele had a defect in spermatogenesis that resulted in small testes associated with increased cell death. The defect was evident as early as postnatal day 21 and was manifested by delayed production of haploid cells. By gene expression profiling, we found that transcript levels for Gal3st1 (also known as cerebroside sulfotransferase [CST]), known to play a crucial role in meiosis, were dramatically reduced inBORISKO testes. We found thatCSTis expressed in testis as a novel testis-specific isoform,CSTform FTS, that has a short exon 1f. We showed that BORIS bound to and activated the promoter ofCSTform FTS. Mutation of the BORIS binding site in the promoter reduced the ability of BORIS to activate the promoter. These findings define transcriptional regulation of CST expression as a critical role for BORIS in spermatogenesis.