The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases.

Abstract:

:Histone methylation regulates chromatin structure and transcription. The recently identified histone demethylase lysine-specific demethylase 1 (LSD1) is chemically restricted to demethylation of only mono- and di- but not trimethylated histone H3 lysine 4 (H3K4me3). We show that the X-linked mental retardation (XLMR) gene SMCX (JARID1C), which encodes a JmjC-domain protein, reversed H3K4me3 to di- and mono- but not unmethylated products. Other SMCX family members, including SMCY, RBP2, and PLU-1, also demethylated H3K4me3. SMCX bound H3K9me3 via its N-terminal PHD (plant homeodomain) finger, which may help coordinate H3K4 demethylation and H3K9 methylation in transcriptional repression. Significantly, several XLMR-patient point mutations reduced SMCX demethylase activity and binding to H3K9me3 peptides, respectively. Importantly, studies in zebrafish and primary mammalian neurons demonstrated a role for SMCX in neuronal survival and dendritic development and a link to the demethylase activity. Our findings thus identify a family of H3K4me3 demethylases and uncover a critical link between histone modifications and XLMR.

journal_name

Cell

journal_title

Cell

authors

Iwase S,Lan F,Bayliss P,de la Torre-Ubieta L,Huarte M,Qi HH,Whetstine JR,Bonni A,Roberts TM,Shi Y

doi

10.1016/j.cell.2007.02.017

subject

Has Abstract

pub_date

2007-03-23 00:00:00

pages

1077-88

issue

6

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(07)00200-0

journal_volume

128

pub_type

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