Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation.
Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation.
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DOI：
10.1007/s10577-008-9005-y
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Grigoryev SA
中科院分区：
文献类型：
--
作者：
Popova EY;Krauss SW;Short SA;Lee G;Villalobos J;Etzell J;Koury MJ;Ney PA;Chasis JA;Grigoryev SA
脊椎动物红染色质终末分化的特点是异染色质逐渐形成，染色质凝聚，在哺乳动物中，最终以核挤出为特征。到目前为止，尽管调节禽类红染色质缩合的机制已经确定，但对哺乳动物红细胞生成过程中的这一过程知之甚少。为了阐明哺乳动物红细胞染色质凝聚的分子基础，我们使用Friend病毒感染的小鼠脾红细胞在体外进行终末分化。从早期和晚期红细胞分离的染色质具有相似的连接子和核心组蛋白水平，只有核小体重复数略有不同，并且没有显著积累已知的发育调节的结构染色质蛋白。然而，随着染色质的浓缩，组蛋白H3(K9)的二甲基化显著增加，而组蛋白H4(K12)的乙酰化显著降低，并与组蛋白甲基化分离。组蛋白脱乙酰酶HDAC5在Friend病毒感染的红细胞分化的终末阶段显著上调。用组蛋白去乙酰化酶抑制剂曲古抑素A处理，可以阻止染色质缩合和核挤出。基于我们的数据，我们提出了一个独特的机制的模型，在该机制中，在着丝粒周围的广泛的组蛋白去乙酰化介导了脊椎动物红细胞中的异染色质缩合，否则将由有核血细胞中发育调节的建筑蛋白来介导。
Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally-regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.
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影响因子：
3.7
作者：
GRIGORYEV, SA;SOLOVIEVA, VO;KRASHENINNIKOV, IA
通讯作者：
KRASHENINNIKOV, IA
影响因子：
4
作者：
Cho, HH;Park, HT;Jung, JS
通讯作者：
Jung, JS
影响因子：
5.3
作者：
Bulynko, Yaroslava A.;Hsing, Lianne C.;Grigoryev, Sergei A.
通讯作者：
Grigoryev, Sergei A.
HP1 蛋白家族：掌控染色质
影响因子：
4
作者：
Eissenberg, JC;Elgin, SCR
通讯作者：
Elgin, SCR
影响因子：
11.4
作者：
Gilbert, N;Boyle, S;Bickmore, WA
通讯作者：
Bickmore, WA