Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis.
Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis.
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DOI：
10.1093/nar/gkq1313
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发表时间：
2011-05
影响因子：
14.9
通讯作者：
Iyer VR
中科院分区：
文献类型：
--
作者：
Lee BK;Bhinge AA;Iyer VR
E2F 转录因子家族在细胞周期进程中发挥重要作用。 E2F4 是 E2F 家族成员，已被认为主要是转录抑制因子，但其结合活性和转录调节功能的范围尚不完全清楚。我们使用 ChIP 测序 (ChIP-seq) 鉴定了大约 16000 个 E2F4 结合位点，这些位点可能调节 7346 个下游靶基因，这些基因在 DNA 修复、细胞周期调节、细胞凋亡和其他过程中具有广泛的功能。虽然所有 E2F4 结合位点的一半 (56%) 发生在转录起始位点 (TSS) 附近，但约 20% 的位点发生在距离任何带注释的 TSS 超过 20 kb 的地方。这些远端位点显示组蛋白修饰，表明 E2F4 可能充当远程调节因子，我们通过对一个子集进行功能实验测定证实了这一点。 E2F4 及其视网膜母细胞瘤 (Rb) 家族转录辅助因子及其结合伴侣 DP-1 的过表达表明，E2F4 既可作为激活剂，又可作为阻抑剂。 E2F4 结合位点也出现在 miRNA 调控元件附近，例如 let-7a 和 mir-17，表明 E2F4 对 miRNA 进行调控。总而言之，我们的全基因组分析提供了 E2F4 多功能作用的证据以及对其功能的深入了解。
The E2F family of transcription factors has important roles in cell cycle progression. E2F4 is an E2F family member that has been proposed to be primarily a repressor of transcription, but the scope of its binding activity and functions in transcriptional regulation is not fully known. We used ChIP sequencing (ChIP-seq) to identify around 16 000 E2F4 binding sites which potentially regulate 7346 downstream target genes with wide-ranging functions in DNA repair, cell cycle regulation, apoptosis, and other processes. While half of all E2F4 binding sites (56%) occurred near transcription start sites (TSSs), ∼20% of sites occurred more than 20 kb away from any annotated TSS. These distal sites showed histone modifications suggesting that E2F4 may function as a long-range regulator, which we confirmed by functional experimental assays on a subset. Overexpression of E2F4 and its transcriptional cofactors of the retinoblastoma (Rb) family and its binding partner DP-1 revealed that E2F4 acts as an activator as well as a repressor. E2F4 binding sites also occurred near regulatory elements for miRNAs such as let-7a and mir-17, suggestive of regulation of miRNAs by E2F4. Taken together, our genome-wide analysis provided evidence of versatile roles of E2F4 and insights into its functions.
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影响因子：
14.9
作者：
Blahnik KR;Dou L;O'Geen H;McPhillips T;Xu X;Cao AR;Iyengar S;Nicolet CM;Ludäscher B;Korf I;Farnham PJ
通讯作者：
Farnham PJ
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
4.3
作者：
Eden E;Lipson D;Yogev S;Yakhini Z
通讯作者：
Yakhini Z
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML