TY - JOUR
T1 - A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation
AU - Kleine-Kohlbrecher, Daniela
AU - Christensen, Jesper
AU - Vandamme, Julien
AU - Abarrategui, Iratxe
AU - Bak, Mads
AU - Tommerup, Niels
AU - Shi, Xiaobing
AU - Gozani, Or
AU - Rappsilber, Juri
AU - Salcini, Anna Elisabetta
AU - Helin, Kristian
N1 - Copyright © 2010 Elsevier Inc. All rights reserved.
PY - 2010/4/23
Y1 - 2010/4/23
N2 - 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.
AB - 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.
U2 - 10.1016/j.molcel.2010.03.002
DO - 10.1016/j.molcel.2010.03.002
M3 - Journal article
C2 - 20346720
SN - 1097-2765
VL - 38
SP - 165
EP - 178
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -