CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription.
CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription.
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DOI：
10.1080/21541264.2015.1095269
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Murphy S
中科院分区：
文献类型：
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作者：
Laitem C;Zaborowska J;Tellier M;Yamaguchi Y;Cao Q;Egloff S;Handa H;Murphy S
CTCF是一种多功能转录因子，在染色质组织和绝缘子功能中具有公认的作用。最近的研究结果也牵连CTCF在控制延长RNA聚合酶（RNAP）II。在这里，我们表明，CTCF敲除废除RNAP II暂停在早期延长检查点的c-myc通过影响招聘的DRB敏感性诱导因子（DSIF）。CTCF敲除还通过影响负延伸因子（NELF）的募集而引起U2 snRNA基因（U2）上的终止缺陷。此外，CTCF是募集正延伸因子B（P-TEF B）所必需的，其磷酸化RNAP II CTD的NELF、DSIF和Ser 2以激活c-myc转录的延伸和snRNA基因特异性3'盒RNA加工信号的识别。这些研究结果牵连CTCF在一个复杂的网络蛋白质：蛋白质/蛋白质：DNA相互作用，并分配一个关键作用CTCF控制RNAP II转录通过延长检查点的蛋白质编码的c-myc和终止位点的非编码U2，通过调节招聘和/或活动的关键球员在这些过程中。
CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation checkpoint of c-myc by affecting recruitment of DRB-sensitivity-inducing factor (DSIF). CTCF knockdown also causes a termination defect on the U2 snRNA genes (U2), by affecting recruitment of negative elongation factor (NELF). In addition, CTCF is required for recruitment of positive elongation factor b (P-TEFb), which phosphorylates NELF, DSIF, and Ser2 of the RNAP II CTD to activate elongation of transcription of c-myc and recognition of the snRNA gene-specific 3’ box RNA processing signal. These findings implicate CTCF in a complex network of protein:protein/protein:DNA interactions and assign a key role to CTCF in controlling RNAP II transcription through the elongation checkpoint of the protein-coding c-myc and the termination site of the non-coding U2, by regulating the recruitment and/or activity of key players in these processes.