• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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

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.

Pubmed ID: 17320160


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



Publication Data

March 23, 2007

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM 071004
  • Agency: NIGMS NIH HHS, Id: GM 58012
  • Agency: NIGMS NIH HHS, Id: GM 70095
  • Agency: PHS HHS, Id: NCI118487
  • Agency: NINDS NIH HHS, Id: NS051255
  • Agency: NINDS NIH HHS, Id: NS41021

Mesh Terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • DNA, Complementary
  • DNA-Binding Proteins
  • Gene Library
  • Histone Demethylases
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • Lysine
  • Mental Retardation, X-Linked
  • Methylation
  • Mice
  • Neoplasm Proteins
  • Neurons
  • Oxidoreductases, N-Demethylating
  • Proteins
  • Retinoblastoma-Binding Protein 2
  • Tumor Suppressor Proteins