组蛋白去甲基化酶PHD锌指蛋白8与神经发育
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国家自然科学基金(30870265),河北省自然科学基金(C2010000410)和广东省男性生殖与遗传重点实验室开放基金(2010002)资助项目


The histone demethylase PHF8 and neural development
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This work was supported by grants from The National Natural Science Foundation of China (30870265), Natural Science Foundation of Hebei Province(C2010000410) and Guangdong Key Laboratory of Male Reproductive Medicine and Genetics(2010002)

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    摘要:

    PHD 锌指蛋白8 (PHF8)是一种Fe2+和α-酮戊二酸依赖的组蛋白赖氨酸去甲基化酶.PHF8属于包含JmjC结构域蛋白家族,在N端还含有一个PHD(plant homeodomain)锌指结构域.人的PHF8基因突变往往破坏组蛋白去甲基化酶活性,从而引发遗传性X-连锁智力迟滞(XLMR)并伴发唇裂的发生.PHF8一方面可催化H3K9me2/1、H4K20me1和H3K27me2的去甲基化,另一方面还通过N端PHD锌指结构域与H3K4me3结合而发挥转录共激活作用.PHF8可调节rRNA和多个涉及神经发育的蛋白编码基因如JARID1C的表达. 这些研究显示PHF8是一种重要的神经发育调节因子,从而拓宽了对组蛋白甲基化与基因表达关联的理解,同时为XLMR疾病的理解提供了新的线索

    Abstract:

    PHF8(PHD finger protein 8) is a Fe2+ and 2-oxoglutarate dependent histone lysine demethylase and belongs to a family of JmjC domain-containing proteins. PHF8 also contains a plant homeodomain (PHD) finger motif in its N-terminus, which involves in transcriptional regulation. PHF8 can demethylate H3K9me2/1, H4K20me1 and H3K27me2 with JmjC domain, and also act as a transcriptional coactivator through binding to H3K4me3 via PHD finger. PHF8 regulates expression of rRNA and many protein-coding genes involved in neural development such as JARID1C. Mutations in human PHF8 which are defective in histone demethylase activity can cause inherited X-linked mental retardation(XLMR) and cleft lip/cleft palate. These researches suggested that PHF8 is an important regulator of neural development, which deepens the understanding of histone methylation with gene expression and provides novel clues to understanding of XLMR.

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郭晓强,沈永青,刘 贝,常彦忠,段相林.组蛋白去甲基化酶PHD锌指蛋白8与神经发育[J].生物化学与生物物理进展,2011,38(4):305-310

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  • 收稿日期:2010-07-29
  • 最后修改日期:2010-09-22
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  • 在线发布日期: 2010-10-19
  • 出版日期: 2011-04-20
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