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Mol Cell. 2014 Feb 20;53(4):672-81. doi: 10.1016/j.molcel.2013.12.029. Epub 2014 Jan 30.
2
Chromatin insulators: linking genome organization to cellular function.染色质绝缘子：将基因组结构与细胞功能联系起来。
Mol Cell. 2013 May 23;50(4):461-74. doi: 10.1016/j.molcel.2013.04.018.
3
Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle.在细胞周期中，DNA 复制相关元件结合因子的基因组定位的动态变化。
Cell Cycle. 2013 May 15;12(10):1605-15. doi: 10.4161/cc.24742. Epub 2013 Apr 25.
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Pre-mRNA splicing is a determinant of nucleosome organization.前体 mRNA 剪接是核小体组织的决定因素。
PLoS One. 2013;8(1):e53506. doi: 10.1371/journal.pone.0053506. Epub 2013 Jan 10.
5
An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting.多梳样蛋白的 H3K36 甲基化结合 Tudor 基序介导 PRC2 复合物的靶向。
Mol Cell. 2013 Feb 7;49(3):571-82. doi: 10.1016/j.molcel.2012.11.026. Epub 2012 Dec 27.
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DiffSplice: the genome-wide detection of differential splicing events with RNA-seq.DiffSplice：基于 RNA-seq 的全基因组差异剪接事件检测。
Nucleic Acids Res. 2013 Jan;41(2):e39. doi: 10.1093/nar/gks1026. Epub 2012 Nov 15.
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Antagonism between MES-4 and Polycomb repressive complex 2 promotes appropriate gene expression in C. elegans germ cells.MES-4 和 Polycomb 抑制复合物 2 之间的拮抗作用促进了线虫生殖细胞中适当的基因表达。
Cell Rep. 2012 Nov 29;2(5):1169-77. doi: 10.1016/j.celrep.2012.09.019. Epub 2012 Oct 25.
8
Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains.基因密度、转录和绝缘子有助于将果蝇基因组分隔成物理域。
Mol Cell. 2012 Nov 9;48(3):471-84. doi: 10.1016/j.molcel.2012.08.031. Epub 2012 Oct 4.
9
Predicting cell-type-specific gene expression from regions of open chromatin.从开放染色质区域预测细胞类型特异性基因表达。
Genome Res. 2012 Sep;22(9):1711-22. doi: 10.1101/gr.135129.111.
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The long-range interaction landscape of gene promoters.基因启动子的远程相互作用景观。
Nature. 2012 Sep 6;489(7414):109-13. doi: 10.1038/nature11279.

绝缘子招募组蛋白甲基转移酶 dMes4 来调节侧翼基因的染色质。

Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes.

机构信息

Laboratoire de Biologie Moléculaire Eucaryote (LBME), CNRS Université de Toulouse (UPS), Toulouse, France.

Systems Biology Center, National Heart, Lung and Blood Institute National Institutes of Health (NIH), Bethesda, MD, USA.

出版信息

EMBO J. 2014 Jul 17;33(14):1599-613. doi: 10.15252/embj.201385965. Epub 2014 Jun 10.

DOI:10.15252/embj.201385965
PMID:24916307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4198054/
Abstract

Chromosomal domains in Drosophila are marked by the insulator-binding proteins (IBPs) dCTCF/Beaf32 and cofactors that participate in regulating long-range interactions. Chromosomal borders are further enriched in specific histone modifications, yet the role of histone modifiers and nucleosome dynamics in this context remains largely unknown. Here, we show that IBP depletion impairs nucleosome dynamics specifically at the promoters and coding sequence of genes flanked by IBP binding sites. Biochemical purification identifies the H3K36 histone methyltransferase NSD/dMes-4 as a novel IBP cofactor, which specifically co-regulates the chromatin accessibility of hundreds of genes flanked by dCTCF/Beaf32. NSD/dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-dependent H3K36 trimethylation, nucleosome positioning, and RNA splicing. Our results unveil a model for how IBPs regulate nucleosome dynamics and gene expression through NSD/dMes-4, which may regulate H3K27me3 spreading. Our data uncover how IBPs dynamically regulate chromatin organization depending on distinct cofactors.

摘要

果蝇中的染色质域由绝缘子结合蛋白 (IBP) dCTCF/Beaf32 和参与调节长距离相互作用的辅助因子标记。染色体边界进一步富含特定的组蛋白修饰，但组蛋白修饰物和核小体动力学在这种情况下的作用在很大程度上仍然未知。在这里，我们表明 IBP 耗竭会特异性地破坏侧翼有 IBP 结合位点的基因的启动子和编码序列处的核小体动力学。生化纯化鉴定出 H3K36 组蛋白甲基转移酶 NSD/dMes-4 作为一种新型的 IBP 共因子，它特异性地共同调节数百个侧翼有 dCTCF/Beaf32 的基因的染色质可及性。NSD/dMes-4 在募集转录激活剂（包括触发 Set2/Hypb 依赖性 H3K36 三甲基化、核小体定位和 RNA 剪接的 DREF）之前预先设定染色质，我们的结果揭示了 IBP 通过 NSD/dMes-4 调节核小体动力学和基因表达的模型，该模型可能调节 H3K27me3 的扩散。我们的数据揭示了 IBP 如何根据不同的共因子动态调节染色质组织。