Transcription-Dependent Generation of a Specialized Chromatin Structure at the TCRβ Locus

Transcription-Dependent Generation of a Specialized Chromatin Structure at the TCRβ Locus
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TCRβ 基因座上特殊染色质结构的转录依赖性生成

DOI:
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发表时间:
2015
影响因子:
4.4
通讯作者:
S. Spicuglia
S. Spicuglia
中科院分区:
医学2区
文献类型:
--
作者:
Joaquin Zacarías;Mohamed Belhocine;Laurent Vanhille;P. Cauchy;Frederic Koch;Aleksandra Pękowska;Romain Fenouil;A. Bergon;M. Gut;I. Gut;D. Eick;J. Imbert;P. Ferrier;J. Andrau;S. Spicuglia

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V(D)J重组在淋巴细胞发育过程中组装Ag受体基因。已知AR基因座处的增强子部分通过增加基因座的染色质可接近性来控制相关等位基因处的V(D)J重组,以允许重组机制接近其染色体底物。然而,是否有一个特定的机制,以诱导染色质可及性在AR基因座仍然不清楚。在这篇文章中,我们强调了一个专门的表观遗传标记,其特征是在整个Dβ-Jβ-Cβ基因片段中具有高和扩展的H3 K4 me 3水平。我们表明,延长H3 K4三甲基化Tcrb基因座依赖于RNA聚合酶II(Pol II)介导的转录。此外,我们发现,包含两个DJCβ簇的基因组区域高度富集Ser 5-磷酸化Pol II和短RNA转录物,这是转录起始和早期转录的两个标志。有趣的是,这些特征与其他一些组织特异性基因共享。我们认为整个DJCβ区域作为转录“起始”平台,因此将Pol II转录的专门机制与扩展的H3 K4三甲基化和高度可及的Dβ和Jβ基因片段联系起来。
V(D)J recombination assembles Ag receptor genes during lymphocyte development. Enhancers at AR loci are known to control V(D)J recombination at associated alleles, in part by increasing chromatin accessibility of the locus, to allow the recombination machinery to gain access to its chromosomal substrates. However, whether there is a specific mechanism to induce chromatin accessibility at AR loci is still unclear. In this article, we highlight a specialized epigenetic marking characterized by high and extended H3K4me3 levels throughout the Dβ-Jβ-Cβ gene segments. We show that extended H3K4 trimethylation at the Tcrb locus depends on RNA polymerase II (Pol II)–mediated transcription. Furthermore, we found that the genomic regions encompassing the two DJCβ clusters are highly enriched for Ser5-phosphorylated Pol II and short-RNA transcripts, two hallmarks of transcription initiation and early transcription. Of interest, these features are shared with few other tissue-specific genes. We propose that the entire DJCβ regions behave as transcription “initiation” platforms, therefore linking a specialized mechanism of Pol II transcription with extended H3K4 trimethylation and highly accessible Dβ and Jβ gene segments.
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