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Recruitment and delivery of the fission yeast Rst2 transcription factor via a local genome structure counteracts repression by Tup1-family corepressors
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2017-06-27 , DOI: 10.1093/nar/gkx555
Ryuta Asada , Miki Umeda , Akira Adachi , Satoshi Senmatsu , Takuya Abe , Hiroshi Iwasaki , Kunihiro Ohta , Charles S. Hoffman , Kouji Hirota

Transcription factors (TFs) determine the transcription activity of target genes and play a central role in controlling the transcription in response to various environmental stresses. Three dimensional genome structures such as local loops play a fundamental role in the regulation of transcription, although the link between such structures and the regulation of TF binding to cis-regulatory elements remains to be elucidated. Here, we show that during transcriptional activation of the fission yeast fbp1 gene, binding of Rst2 (a critical C2H2 zinc-finger TF) is mediated by a local loop structure. During fbp1 activation, Rst2 is first recruited to upstream-activating sequence 1 (UAS1), then it subsequently binds to UAS2 (a critical cis-regulatory site located approximately 600 base pairs downstream of UAS1) through a loop structure that brings UAS1 and UAS2 into spatially close proximity. Tup11/12 (the Tup-family corepressors) suppress direct binding of Rst2 to UAS2, but this suppression is counteracted by the recruitment of Rst2 at UAS1 and following delivery to UAS2 through a loop structure. These data demonstrate a previously unappreciated mechanism for the recruitment and expansion of TF-DNA interactions within a promoter mediated by local three-dimensional genome structures and for timely TF-binding via counteractive regulation by the Tup-family corepressors.

中文翻译:

通过局部基因组结构招募和传递裂变酵母Rst2转录因子抵消了Tup1家族共表达的抑制

转录因子(TFs)决定目标基因的转录活性,并在响应各种环境压力的转录控制中发挥重要作用。三维基因组结构(例如局部环)在转录调控中起着基本作用,尽管这种结构与TF与顺式调控元件结合的调控之间的联系仍有待阐明。在这里,我们显示在裂变酵母fbp1基因的转录激活过程中,Rst2(关键的C 2 H 2锌指TF)的结合是由局部环结构介导的。在fbp1期间激活时,首先将Rst2募集到上游激活序列1(UAS1),然后通过循环结构将UAS1和UAS2紧密结合到UAS2(UAS1下游约600个碱基对的关键顺式调控位点)上。接近。Tup11 / 12(Tup家族的核心抑制剂)抑制Rst2与UAS2的直接结合,但这种抑制作用是通过在UAS1募集Rst2并通过环结构递送至UAS2来抵消的。这些数据证明了以前未知的机制,用于由局部三维基因组结构介导的启动子内的TF-DNA相互作用的募集和扩展,以及通过Tup家族的核心抑制因子的抗性调控及时进行TF结合。
更新日期:2017-09-21
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