Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis.
Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis.
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DOI：
10.1016/j.celrep.2013.11.044
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发表时间：
2014-01-16
期刊：
影响因子：
8.8
通讯作者：
Godley LA
中科院分区：
文献类型：
--
作者：
Madzo J;Liu H;Rodriguez A;Vasanthakumar A;Sundaravel S;Caces DBD;Looney TJ;Zhang L;Lepore JB;Macrae T;Duszynski R;Shih AH;Song CX;Yu M;Yu Y;Grossman R;Raumann B;Verma A;He C;Levine RL;Lavelle D;Lahn BT;Wickrema A;Godley LA
造血干细胞分化涉及自我更新基因的沉默和特定转录程序的诱导。多个共价胞嘧啶修饰的鉴定提出了这些衍生碱基如何影响干细胞定向的问题。使用复制性原代人类造血干/祖细胞分化系统，我们证明了干细胞定向和分化为红细胞系年龄期间 5-羟甲基胞嘧啶 (5-hmC) 的动态变化。在整个红系分化过程中维持或获得 5-hmC 密度的基因组位点包含红系转录因子和一些先前未被识别为红系特异性因子的因子的结合位点。 5-hmC 的功能重要性通过红系分化受损、髓系潜能增强以及具有 TET 甲基胞嘧啶双加氧酶 2 (TET2) 突变的白血病患者来源的 CD34+ 干细胞/早期祖细胞中 5-hmC 模式被破坏来证明。因此，化学缀合和亲和纯化富含 5-hmC 的序列，然后进行测序，可作为破译干细胞定型和沿特定谱系分化期间基因表达功能影响的资源。
Hematopoietic stem cell differentiation involves the silencing of self-renewal genes and induction of a specific transcriptional program. Identification of multiple covalent cytosine modifications raises the question of how these derivatized bases influence stem cell commitment. Using a replicative primary human hematopoietic stem/progenitor cell differentiation system, we demonstrate dynamic changes of 5-hydroxymethylcytosine (5-hmC) during stem cell commitment and differentiation to the erythroid line-age. Genomic loci that maintain or gain 5-hmC density throughout erythroid differentiation contain binding sites for erythroid transcription factors and several factors not previously recognized as erythroid-specific factors. The functional importance of 5-hmC was demonstrated by impaired erythroid differentiation, with augmentation of myeloid potential, and disrupted 5-hmC patterning in leukemia patient-derived CD34+ stem/early progenitor cells with TET methylcytosine dioxygenase 2 (TET2) mutations. Thus, chemical conjugation and affinity purification of 5-hmC-enriched sequences followed by sequencing serve as resources for deciphering functional implications for gene expression during stem cell commitment and differentiation along a particular lineage.
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影响因子：
5.3
作者：
Kang, Yoon-A;Sanalkumar, Rajendran;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
在体内小鼠红细胞生成过程中，全局DNA脱甲基化。
DOI：
10.1126/science.1207306
发表时间：
2011-11-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shearstone JR;Pop R;Bock C;Boyle P;Meissner A;Socolovsky M
通讯作者：
Socolovsky M
影响因子：
50.3
作者：
Moran-Crusio K;Reavie L;Shih A;Abdel-Wahab O;Ndiaye-Lobry D;Lobry C;Figueroa ME;Vasanthakumar A;Patel J;Zhao X;Perna F;Pandey S;Madzo J;Song C;Dai Q;He C;Ibrahim S;Beran M;Zavadil J;Nimer SD;Melnick A;Godley LA;Aifantis I;Levine RL
通讯作者：
Levine RL