TRA-1 ChIP-seq reveals regulators of sexual differentiation and multilevel feedback in nematode sex determination
TRA-1 ChIP-seq reveals regulators of sexual differentiation and multilevel feedback in nematode sex determination
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DOI：
10.1073/pnas.1312087110
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发表时间：
2013-10-01
影响因子：
11.1
通讯作者：
Zarkower, David
中科院分区：
文献类型：
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作者：
Berkseth, Matt;Ikegami, Kohta;Zarkower, David
性调控者如何将全球性命运转化为适当的局部性分化事件，可能是性发育中最不为人所知的方面。在这里，我们使用ChIP和深度测序（ChIP-seq）来确定线虫全局性调节因子Transformer 1 （TRA-1）的直接靶点，TRA-1是一种转录因子，在生物范围和细胞特异性性调节之间起作用，控制所有性别特异性的体细胞分化事件。我们在秀丽隐杆线虫中鉴定了184个TRA-1结合位点，其中许多位点具有时间和/或组织特异性的TRA-1关联。我们还在相关的briggsae隐杆线虫中鉴定了78个tra -1结合位点，其中19个在两个物种之间保守。一些含有tra -1结合位点的DNA片段驱动男性特异性表达模式，一些靠近tra -1结合位点的基因的RNAi缺失导致男性性发育缺陷。TRA-1结合到一些异慢性调控基因附近的位点，其中一些基因驱动男性特异性表达，这表明TRA-1对发育时间施加了性别特异性。我们还发现了TRA-1反馈调节全球性别决定途径的证据：TRA-1结合其自身位点和多个上游雄性化基因的位点，并且这些关联大部分在C. briggsae中保守。因此，TRA-1通过加强性别决定决定和指导下游性别分化事件来协调性发育。
How sexual regulators translate global sexual fate into appropriate local sexual differentiation events is perhaps the least understood aspect of sexual development. Here we have used ChIP followed by deep sequencing (ChIP-seq) to identify direct targets of the nematode global sexual regulator Transformer 1 (TRA-1), a transcription factor acting at the interface between organism-wide and cell-specific sexual regulation to control all sex-specific somatic differentiation events. We identified 184 TRA-1-binding sites in Caenorhabditis elegans, many with temporal-and/or tissue-specific TRA-1 association. We also identified 78 TRA-1-binding sites in the related nematode Caenorhabditis briggsae, 19 of which are conserved between the two species. Some DNA segments containing TRA-1-binding sites drive male-specific expression patterns, and RNAi depletion of some genes adjacent to TRA-1-binding sites results in defects in male sexual development. TRA-1 binds to sites adjacent to a number of heterochronic regulatory genes, some of which drive male-specific expression, suggesting that TRA-1 imposes sex specificity on developmental timing. We also found evidence for TRA-1 feedback regulation of the global sex-determination pathway: TRA-1 binds its own locus and those of multiple upstream masculinizing genes, and most of these associations are conserved in C. briggsae. Thus, TRA-1 coordinates sexual development by rein-forcing the sex-determination decision and directing downstream sexual differentiation events.