组蛋白去甲基化酶PHD锌指蛋白8与神经发育  

The Histone Demethylase PHF8 and Neural Development

作　　者：郭晓强[1,2,3] 沈永青[1] 刘贝[1] 常彦忠[1] 段相林[1] 

机构地区：[1]河北师范大学生命科学学院铁代谢分子生物学研究室,石家庄050061 [2]解放军白求恩军医学院生化教研室,石家庄050081 [3]北京大学深圳医院男性生殖与遗传广东省重点实验室,深圳518036

出　　处：《生物化学与生物物理进展》2011年第4期305-310,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(30870265);河北省自然科学基金(C2010000410);广东省男性生殖与遗传重点实验室开放基金(2010002)资助项目~~

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(planthomeodomain)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质编码基因如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.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.

关 键 词：组蛋白去甲基化酶 PHD锌指蛋白8 X-连锁智力迟滞 神经发育 

分 类 号：Q55[生物学—生物化学] Q42