The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation
Autor: | Rui Fang, Anjana Rao, Fumiko Shimizu, Pinchao Mei, Jing Li, Yujiang Shi, Mamta Tahiliani, Thiago Leonor, Michael S. Rutenberg |
---|---|
Rok vydání: | 2007 |
Předmět: |
Chromatin Immunoprecipitation
Spodoptera Biology Methylation Substrate Specificity Histones Histone H1 Histone H2A Animals Humans Histone code Promoter Regions Genetic Histone demethylase activity Histone Demethylases Neurons Genetics Multidisciplinary Histone deacetylase 2 Proteins Oxidoreductases N-Demethylating Chromatin Repressor Proteins Gene Expression Regulation Multiprotein Complexes Histone methyltransferase Mental Retardation X-Linked RNA Interference Chromatin immunoprecipitation HeLa Cells Transcription Factors |
Zdroj: | Nature. 447:601-605 |
ISSN: | 1476-4687 0028-0836 |
Popis: | Gene transcription is critically influenced by chromatin structure and the modification status of histone tails. Methylation of lysine residues in histone tails is dynamically regulated by the opposing activities of histone methyltransferases and histone demethylases. Here we show that JARID1C/SMCX, a JmjC-domain-containing protein implicated in X-linked mental retardation and epilepsy, possesses H3K4 tri-demethylase activity and functions as a transcriptional repressor. An SMCX complex isolated from HeLa cells contains additional chromatin modifiers (the histone deacetylases HDAC1 and HDAC2, and the histone H3K9 methyltransferase G9a) and the transcriptional repressor REST, suggesting a direct role for SMCX in chromatin dynamics and REST-mediated repression. Chromatin immunoprecipitation reveals that SMCX and REST co-occupy the neuron-restrictive silencing elements in the promoters of a subset of REST target genes. RNA-interference-mediated depletion of SMCX derepresses several of these targets and simultaneously increases H3K4 trimethylation at the sodium channel type 2A (SCN2A) and synapsin I (SYN1) promoters. We propose that loss of SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation. |
Databáze: | OpenAIRE |
Externí odkaz: |