TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.
TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.
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DOI：
10.1038/srep32069
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发表时间：
2016-08-31
影响因子：
4.6
通讯作者：
Davidson I
中科院分区：
文献类型：
--
作者：
Martianov I;Velt A;Davidson G;Choukrallah MA;Davidson I
哺乳动物基因组编码两个与TBP相关的基因，TBP相关因子2和3(TRF2和TRF3)。雄性TRF2−/−小鼠是不育的，其特征是从单倍体晚期精子细胞向早期伸长精子细胞转变时精子发生停滞。尽管有这些特征，但小鼠TRF2的分子功能仍然没有得到很好的描述，并且没有直接证据表明它是真正的染色质结合转录因子。我们发现TRF2与TFIIA或睾丸表达的类似ALF形成稳定的复合体，通过热休克蛋白伴随在细胞质中。我们首次证明TRF2与TBP、Taf71和RNA聚合酶II一起被招募为活性单倍体细胞启动子。RNA-seq分析发现，在精子发生的第一波中，单倍体精子细胞中激活了一组基因，这些基因的表达被TRF2失活下调。因此，我们建议TRF2被招募到预起始复合体中，作为TFIIA/ALF的睾丸特异性亚基，与TBP和Taf71协同促进单倍体细胞基因的表达。
Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2−/− mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression.
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