Barrier-to-Autointegration Factor influences specific histone modifications
Barrier-to-Autointegration Factor influences specific histone modifications
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DOI：
10.4161/nucl.2.6.17960
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发表时间：
2011-11-01
期刊：
影响因子：
3.7
通讯作者：
Wilson, Katherine L.
中科院分区：
文献类型：
--
作者：
de Oca, Rocio Montes;Andreassen, Paul R.;Wilson, Katherine L.
核被膜或核“纤层”网络的缺陷会引起疾病，并可能扰乱组蛋白翻译后（表观遗传）调控。自整合屏障因子（BAF）是一种重要的但神秘的纤层组分，其直接结合纤层蛋白、LEM结构域蛋白、DNA和组蛋白H3。我们报告说，BAF与核酸酶消化的单核小体共纯化，并与体内修饰的组蛋白。BAF过表达显著降低了18%的整体组蛋白H3乙酰化。在稳定过表达BAF 3倍的细胞中，沉默标记H3-K27-Me 1/3和活性标记H4-K16-Ac和H4-Ac 5显著减少。对于沉默标记H3-K9-Me 3、活性标记H3-K4-Me 2、H3-K9/K14-Ac和H4-K5-Ac以及与活性和沉默染色质两者相关的标记（H3-K79-Me 2）也观察到显著增加。其他增加（H3-S10-P、H3-S28-P和沉默标记H3-K9-Me 2）未达到统计学显著性。BAF过表达也显著影响细胞周期分布。此外，BAF在体内与SET/I2 PP 2A（蛋白磷酸酶2A抑制剂;阻断H3去磷酸化）和G9 a（H3-K9甲基转移酶）相关，但与HDAC 1或HAT无可检测的相关性。这些发现揭示了BAF作为一种新的表观遗传调节因子，并讨论了BAF缺乏症表型，其中包括遗传性早衰综合征和胚胎干细胞多能性丧失。
Defects in the nuclear envelope or nuclear 'lamina' networks cause disease and can perturb histone posttranslational (epigenetic) regulation. Barrier-to-Autointegration Factor (BAF) is an essential but enigmatic lamina component that binds lamins, LEM-domain proteins, DNA and histone H3 directly. We report that BAF copurified with nuclease-digested mononucleosomes and associated with modified histones in vivo. BAF overexpression significantly reduced global histone H3 acetylation by 18%. In cells that stably overexpressed BAF 3-fold, silencing mark H3-K27-Me1/3 and active marks H4-K16-Ac and H4-Ac5 decreased significantly. Significant increases were also seen for silencing mark H3-K9-Me3, active marks H3-K4-Me2, H3-K9/K14-Ac and H4-K5-Ac and a mark (H3-K79-Me2) associated with both active and silent chromatin. Other increases (H3-S10-P, H3-S28-P and silencing mark H3-K9-Me2) did not reach statistical significance. BAF overexpression also significantly influenced cell cycle distribution. Moreover, BAF associated in vivo with SET/I2PP2A (protein phosphatase 2A inhibitor; blocks H3 dephosphorylation) and G9a (H3-K9 methyltransferase), but showed no detectable association with HDAC1 or HATs. These findings reveal BAF as a novel epigenetic regulator and are discussed in relation to BAF deficiency phenotypes, which include a hereditary progeria syndrome and loss of pluripotency in embryonic stem cells.