A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation

被引：173

作者：

Kleine-Kohlbrecher, Daniela ^{[1
]}

Christensen, Jesper ^{[1
]}

Vandamme, Julien ^{[1
]}

Abarrategui, Iratxe ^{[1
]}

Bak, Mads ^{[2
]}

Tommerup, Niels ^{[2
]}

Shi, Xiaobing ^{[3
]}

Gozani, Or ^{[4
]}

Rappsilber, Juri ^{[5
]}

Salcini, Anna Elisabetta ^{[1
]}

Helin, Kristian ^{[1
]}

机构：

[1] Univ Copenhagen, Ctr Epigenet, BRIC, DK-2200 Copenhagen, Denmark

[2] Univ Copenhagen, Dept Cellular & Mol Med, Wilhelm Johannsen Ctr Funct Genome Res, DK-2200 Copenhagen N, Denmark

[3] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[4] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA

[5] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland

来源：

MOLECULAR CELL | 2010年 / 38卷 / 02期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

TARGET GENES; MUTATIONS; IDENTIFICATION; TRIMETHYLATION; PLASTICITY; PROTEINS; FINGER; SCREEN; FAMILY; XLMR;

D O I：

10.1016/j.molcel.2010.03.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionally link the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionally linked in pathways, causing the complex phenotypes observed in patients developing MR.

引用

页码：165 / 178

页数：14

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