Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

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

ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression.

Dynamic regulation of diverse nuclear processes is intimately linked to covalent modifications of chromatin. Much attention has focused on methylation at lysine 4 of histone H3 (H3K4), owing to its association with euchromatic genomic regions. H3K4 can be mono-, di- or tri-methylated. Trimethylated H3K4 (H3K4me3) is preferentially detected at active genes, and is proposed to promote gene expression through recognition by transcription-activating effector molecules. Here we identify a novel class of methylated H3K4 effector domains--the PHD domains of the ING (for inhibitor of growth) family of tumour suppressor proteins. The ING PHD domains are specific and highly robust binding modules for H3K4me3 and H3K4me2. ING2, a native subunit of a repressive mSin3a-HDAC1 histone deacetylase complex, binds with high affinity to the trimethylated species. In response to DNA damage, recognition of H3K4me3 by the ING2 PHD domain stabilizes the mSin3a-HDAC1 complex at the promoters of proliferation genes. This pathway constitutes a new mechanism by which H3K4me3 functions in active gene repression. Furthermore, ING2 modulates cellular responses to genotoxic insults, and these functions are critically dependent on ING2 interaction with H3K4me3. Together, our findings establish a pivotal role for trimethylation of H3K4 in gene repression and, potentially, tumour suppressor mechanisms.

Pubmed ID: 16728974


  • Shi X
  • Hong T
  • Walter KL
  • Ewalt M
  • Michishita E
  • Hung T
  • Carney D
  • Peña P
  • Lan F
  • Kaadige MR
  • Lacoste N
  • Cayrou C
  • Davrazou F
  • Saha A
  • Cairns BR
  • Ayer DE
  • Kutateladze TG
  • Shi Y
  • Côté J
  • Chua KF
  • Gozani O



Publication Data

July 6, 2006

Associated Grants

  • Agency: Canadian Institutes of Health Research, Id: 64289-1
  • Agency: NIGMS NIH HHS, Id: R01 GM060415
  • Agency: NIGMS NIH HHS, Id: R01 GM060415-06
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Amino Acid Motifs
  • Chromatin
  • Gene Silencing
  • Histone Deacetylases
  • Histones
  • Homeodomain Proteins
  • Lysine
  • Methylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Tumor Suppressor Proteins