PUBLICATION
The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases
- Authors
- Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M., and Shi, Y.
- ID
- ZDB-PUB-100427-27
- Date
- 2007
- Source
- Cell 128(6): 1077-1088 (Journal)
- Registered Authors
- Bayliss, Peter, Roberts, Thomas M.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Survival
- DNA, Complementary
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Gene Library
- Histone Demethylases
- Histone-Lysine N-Methyltransferase/genetics
- Histone-Lysine N-Methyltransferase/metabolism
- Histones/chemistry
- Histones/metabolism*
- Humans
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Jumonji Domain-Containing Histone Demethylases
- Lysine/metabolism
- Mental Retardation, X-Linked/genetics*
- Methylation
- Mice
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism
- Neurons/cytology
- Neurons/metabolism
- Oxidoreductases, N-Demethylating/genetics*
- Oxidoreductases, N-Demethylating/metabolism
- Proteins/genetics*
- Proteins/metabolism
- Retinoblastoma-Binding Protein 2
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism
- PubMed
- 17320160 Full text @ Cell
Citation
Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M., and Shi, Y. (2007) The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 128(6):1077-1088.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping