Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins.

Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins.
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DOI:
10.1074/jbc.m807818200
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发表时间:
2009-03-27
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Reinberg D
Reinberg D
中科院分区:
其他
文献类型:
--
作者:
Trojer P;Zhang J;Yonezawa M;Schmidt A;Zheng H;Jenuwein T;Reinberg D

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连接体组蛋白H1一般参与染色质结构的建立。然而,在人类的7种体细胞H1亚型中,一些也与局部基因表达的调控有关。组蛋白H1同型4 (H1.4)抑制转录,其赖氨酸残基26 (Lys26)在这方面起重要作用。已知H1.4 k26在体内甲基化和乙酰化,但负责这些翻译后修饰的酶和促进H1.4在染色质上驻留的调节线索的特征很少。本研究报道,在体外和体内,共染色质组蛋白赖氨酸甲基转移酶G9a/KMT1C介导H1.4K26单甲基化和二甲基化,从而为染色质结合蛋白HP1和L3MBTL1提供识别表面。此外,我们证明了G9a促进H1沉积,并且是H1在染色质上保留所必需的。我们还确定了朱蒙菌c型组蛋白去甲基化酶的JMJD2/KDM4亚家族成员负责去除H1.4K26甲基化。
The linker histone H1 generally participates in the establishment of chromatin structure. However, of the seven somatic H1 isotypes in humans some are also implicated in the regulation of local gene expression. Histone H1 isotype 4 (H1.4) represses transcription, and its lysine residue 26 (Lys26) was found to be important in this aspect. H1.4K26 is known to be methylated and acetylated in vivo, but the enzymes responsible for these post-translational modifications and the regulatory cues that promote H1.4 residence on chromatin are poorly characterized. Here we report that the euchromatic histone lysine methyltransferase G9a/KMT1C mediates H1.4K26 mono- and dimethylation in vitro and in vivo and thereby provides a recognition surface for the chromatin-binding proteins HP1 and L3MBTL1. Moreover, we show evidence that G9a promotes H1 deposition and is required for retention of H1 on chromatin. We also identify members of the JMJD2/KDM4 subfamily of jumonji-C type histone demethylases as being responsible for the removal of H1.4K26 methylation.