Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules.
Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules.
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DOI：
10.1101/gr.136507.111
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发表时间：
2012-11
期刊：
影响因子：
7
通讯作者：
Flicek P
中科院分区：
文献类型：
--
作者：
Faure AJ;Schmidt D;Watt S;Schwalie PC;Wilson MD;Xu H;Ramsay RG;Odom DT;Flicek P
粘附素蛋白复合体通过与组织特异性位点的主要调控因子共定位，以不依赖于CTCF的方式参与转录调控。转录调控涉及多个转录因子的协同作用，而粘附素在组合转录因子结合中的作用尚不清楚。为了研究体内的粘附素-非CTCF结合事件，我们使用CHIP-SEQ定位了粘附素和CTCF，以及一系列组织特异性和普遍存在的转录调控因子。我们观察到不同的TF结合的数量和CnC位点的存在之间存在正相关。与基因组中粘附素和CTCF共定位的区域不同，CnC位点与主调节因子和增强子标记的结合相吻合，并与肝脏特异性表达基因显著相关。我们还表明，粘附素的存在部分解释了通常观察到的TF基序分数和CHIP信号之间的差异。来自野生型细胞的这些统计分析的证据，以及与Rad21-粘附素单倍体不足的小鼠肝脏的Tf结合图谱的比较，表明粘附素有助于稳定大的蛋白质-DNA复合体。最后，我们观察到在启动子及其附近的粘附素结合增强子上存在镜像的CTCF结合事件，这与表达水平的升高有关。
The cohesin protein complex contributes to transcriptional regulation in a CTCF-independent manner by colocalizing with master regulators at tissue-specific loci. The regulation of transcription involves the concerted action of multiple transcription factors (TFs) and cohesin's role in this context of combinatorial TF binding remains unexplored. To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver. We observe a positive correlation between the number of distinct TFs bound and the presence of CNC sites. In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes. We also show that cohesin presence partially explains the commonly observed discrepancy between TF motif score and ChIP signal. Evidence from these statistical analyses in wild-type cells, and comparisons to maps of TF binding in Rad21-cohesin haploinsufficient mouse liver, suggests that cohesin helps to stabilize large protein–DNA complexes. Finally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels.
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DOI：
10.1083/jcb.200111002
发表时间：
2002-02-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Anderson DE;Losada A;Erickson HP;Hirano T
通讯作者：
Hirano T
影响因子：
16
作者：
Haering, CH;Löwe, J;Nasmyth, K
通讯作者：
Nasmyth, K
影响因子：
11.4
作者：
Bartkuhn, Marek;Straub, Tobias;Renkawitz, Rainer
通讯作者：
Renkawitz, Rainer
影响因子：
7
作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas