Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.
Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.
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DOI：
10.1093/nar/gks595
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发表时间：
2012-09-01
影响因子：
14.9
通讯作者：
Salbert G
中科院分区：
文献类型：
--
作者：
Sérandour AA;Avner S;Oger F;Bizot M;Percevault F;Lucchetti-Miganeh C;Palierne G;Gheeraert C;Barloy-Hubler F;Péron CL;Madigou T;Durand E;Froguel P;Staels B;Lefebvre P;Métivier R;Eeckhoute J;Salbert G
增强子是发育控制的转录调控区，其活性通过组蛋白修饰或组蛋白变体沉积来调节。在这项研究中，我们通过全基因组作图表明，新发现的脱氧核糖核酸（DNA）修饰5-羟甲基胞嘧啶（5 hmC）与转录因子结合到远端调控位点在小鼠P19细胞神经分化和小鼠3 T3-L1细胞脂肪细胞分化过程中动态相关。功能注释显示，获得5 hmC的区域与当P19细胞经历神经分化时在神经组织中表达的基因或当3 T3-L1细胞经历脂肪细胞分化时在脂肪组织中表达的基因相关。此外，在P19细胞中，获得5 hmC的远端区域与H3 K4 me 2和H3 K27 ac一起表现为分化依赖的转录增强子。鉴定的区域富含调节特定细胞命运的转录因子的基序，例如P19细胞中的Meis 1和3 T3-L1细胞中的PPARγ。因此，一部分羟甲基化Meis 1位点与5-甲基胞嘧啶羟化酶Tet 1的动态参与相关。此外，所选增强子的胞嘧啶羟甲基化的动力学研究表明，DNA羟甲基化是增强子激活的早期事件。因此，在细胞特异性远端调控区获得5 hmC可能代表增强子向活性状态进展的主要事件，并参与组织特异性基因的选择性激活。
Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.
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影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
14.9
作者：
Jin SG;Kadam S;Pfeifer GP
通讯作者：
Pfeifer GP
人类胰岛中的开放染色质图。
影响因子：
30.8
作者：
Gaulton, Kyle J.;Nammo, Takao;Pasquali, Lorenzo;Simon, Jeremy M.;Giresi, Paul G.;Fogarty, Marie P.;Panhuis, Tami M.;Mieczkowski, Piotr;Secchi, Antonio;Bosco, Domenico;Berney, Thierry;Montanya, Eduard;Mohlke, Karen L.;Lieb, Jason D.;Ferrer, Jorge
通讯作者：
Ferrer, Jorge
影响因子：
30.8
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
通讯作者：
Wolffe, AP