Dynamic transitions in RNA polymerase II density profiles during transcription termination.
Dynamic transitions in RNA polymerase II density profiles during transcription termination.
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DOI：
10.1101/gr.138057.112
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发表时间：
2012-08
期刊：
影响因子：
7
通讯作者：
Carmo-Fonseca M
中科院分区：
文献类型：
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作者：
Grosso AR;de Almeida SF;Braga J;Carmo-Fonseca M
真核生物蛋白质编码基因由RNA聚合酶II(RNAPII)转录，经过三个主要阶段：起始、延伸和终止。最近使用染色质免疫沉淀和高通量测序相结合的研究表明，RNAPII分子在3‘端的密度比基因体高。在这里，我们表明，这种观点是有偏见的，因为平均密度分布的“后生”分析。事实上，大多数基因在转录终止期间几乎没有聚合酶的积累，如果有的话。与未富集的基因相比，在3‘端积累RNAPII的基因更短，在下游序列元件中更频繁地含有典型的多聚腺苷酸化信号AATAAA和富含G的基序，并且具有更高的表达水平。在1%到4%的活跃转录基因中，3‘端富含的RNAPII在Ser5上被磷酸化，我们提供的证据表明这些基因的启动子和终止子区域并列。我们还发现RNAPII的积累与核小体组织之间存在显著的相关性，这表明在Poly(A)位点之后核小体的存在导致聚合酶的暂停，导致它们的积累。然而，我们进一步观察到，基因3‘端的核小体占有率是动态的，并与RNAPII密度相关。综上所述，我们的结果为转录终止提供了新的见解，这是一个基本过程，仍然是转录周期中最不被了解的阶段之一。
Eukaryotic protein-coding genes are transcribed by RNA polymerase II (RNAPII) through a cycle composed of three main phases: initiation, elongation, and termination. Recent studies using chromatin immunoprecipitation coupled to high-throughput sequencing suggest that the density of RNAPII molecules is higher at the 3′-end relative to the gene body. Here we show that this view is biased due to averaging density profiles for “metagene” analysis. Indeed, the majority of genes exhibit little, if any, detectable accumulation of polymerases during transcription termination. Compared with genes with no enrichment, genes that accumulate RNAPII at the 3′-end are shorter, more frequently contain the canonical polyadenylation [poly(A)] signal AATAAA and G-rich motifs in the downstream sequence element, and have higher levels of expression. In 1% to 4% of actively transcribing genes, the RNAPII enriched at the 3′-end is phosphorylated on Ser5, and we provide evidence suggesting that these genes have their promoter and terminator regions juxtaposed. We also found a striking correlation between RNAPII accumulation and nucleosome organization, suggesting that the presence of nucleosomes after the poly(A) site induces pausing of polymerases, leading to their accumulation. Yet we further observe that nucleosome occupancy at the 3′-end of genes is dynamic and correlates with RNAPII density. Taken together, our results provide novel insight to transcription termination, a fundamental process that remains one of the least understood stages of the transcription cycle.
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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
影响因子：
64.5
作者：
Hah N;Danko CG;Core L;Waterfall JJ;Siepel A;Lis JT;Kraus WL
通讯作者：
Kraus WL
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1126/science.1172926
发表时间：
2009-07-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hodges C;Bintu L;Lubkowska L;Kashlev M;Bustamante C
通讯作者：
Bustamante C
影响因子：
64.8
作者：
通讯作者：
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