Epigenetic regulation of myogenic gene expression by heterochromatin protein 1 alpha.
Epigenetic regulation of myogenic gene expression by heterochromatin protein 1 alpha.
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DOI：
10.1371/journal.pone.0058319
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
MacLellan WR
中科院分区：
文献类型：
--
作者：
Sdek P;Oyama K;Angelis E;Chan SS;Schenke-Layland K;MacLellan WR
异染色质蛋白1(HP1)是一种重要的异染色质相关蛋白，通常参与基因沉默的表观遗传调控。然而，最近的报道表明，HP1也可以在某些情况下激活基因表达，包括分化。为了探讨三个哺乳动物Hp1家族成员(α，β和γ)在骨骼肌中的作用，我们分别干扰了它们在骨骼肌细胞分化过程中的表达。在hp1的三种亚型中，hp1α仅在成肌细胞中特异性地表达生肌基因。Hp1α基因敲除导致骨骼肌特异性基因转录缺陷，包括Lbx1、MyoD和Mygenin。Hp1α与生肌基因的基因组区域结合，Hp1α的缺失导致组蛋白H3赖氨酸9三甲基化(H3K9me3)在这些位置矛盾地增加。H3K9去甲基酶JHDM3A也以Hp1α依赖的方式与成肌细胞的生肌基因的基因组区域结合。JHDM3A与Hp1α相互作用，并在成肌细胞中敲除JHDM3A，重现了Hp1α缺失导致的生肌基因转录下降。这些结果提出了一种新的机制，通过与去甲基酶JHDM3A相互作用来激活依赖于hp1α的基因，并且hp1α是维持成肌细胞肌源性基因表达所必需的。
Heterochromatin protein 1 (HP1) is an essential heterochromatin-associated protein typically involved in the epigenetic regulation of gene silencing. However, recent reports have demonstrated that HP1 can also activate gene expression in certain contexts including differentiation. To explore the role of each of the three mammalian HP1 family members (α, β and γ) in skeletal muscle, their expression was individually disrupted in differentiating skeletal myocytes. Among the three isoforms of HP1, HP1α was specifically required for myogenic gene expression in myoblasts only. Knockdown of HP1α led to a defect in transcription of skeletal muscle-specific genes including Lbx1, MyoD and myogenin. HP1α binds to the genomic region of myogenic genes and depletion of HP1α results in a paradoxical increase in histone H3 lysine 9 trimethylation (H3K9me3) at these sites. JHDM3A, a H3K9 demethylase also binds to myogenic gene’s genomic regions in myoblasts in a HP1α-dependent manner. JHDM3A interacts with HP1α and knockdown of JHDM3A in myoblasts recapitulates the decreased myogenic gene transcription seen with HP1α depletion. These results propose a novel mechanism for HP1α-dependent gene activation by interacting with the demethylase JHDM3A and that HP1α is required for maintenance of myogenic gene expression in myoblasts.
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影响因子：
21.3
作者：
Lomberk, G;Bensi, D;Urrutia, R
通讯作者：
Urrutia, R
影响因子：
11.4
作者：
Mennerich, D;Braun, T
通讯作者：
Braun, T
影响因子：
16
作者：
Lu, JR;McKinsey, TA;Olson, EN
通讯作者：
Olson, EN
影响因子：
10.5
作者：
Cammas, F;Herzog, M;Losson, R
通讯作者：
Losson, R
DOI：
10.1073/pnas.211303598
发表时间：
2001-09-25
影响因子：
11.1
作者：
Hwang, KK;Eissenberg, JC;Worman, HJ
通讯作者：
Worman, HJ