Disruption of the interaction between transcriptional intermediary factor 1{beta} and heterochromatin protein 1 leads to a switch from DNA hyper- to hypomethylation and H3K9 to H3K27 trimethylation on the MEST promoter correlating with gene reactivation

Mol Biol Cell. 2009 Jan;20(1):296-305. doi: 10.1091/mbc.e08-05-0510. Epub 2008 Oct 15.


Here, we identified the imprinted mesoderm-specific transcript (MEST) gene as an endogenous TIF1beta primary target gene and demonstrated that transcriptional intermediary factor (TIF) 1beta, through its interaction with heterochromatin protein (HP) 1, is essential in establishing and maintaining a local heterochromatin-like structure on MEST promoter region characterized by H3K9 trimethylation and hypoacetylation, H4K20 trimethylation, DNA hypermethylation, and enrichment in HP1 that correlates with preferential association to foci of pericentromeric heterochromatin and transcriptional repression. On disruption of the interaction between TIF1beta and HP1, TIF1beta is released from the promoter region, and there is a switch from DNA hypermethylation and histone H3K9 trimethylation to DNA hypomethylation and histone H3K27 trimethylation correlating with rapid reactivation of MEST expression. Interestingly, we provide evidence that the imprinted MEST allele DNA methylation is insensitive to TIF1beta loss of function, whereas the nonimprinted allele is regulated through a distinct TIF1beta-DNA methylation mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Methylation*
  • Genomic Imprinting*
  • Heterochromatin / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proteins / genetics*
  • Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Nuclear Proteins
  • Protein Isoforms
  • Proteins
  • Transcription Factors
  • mesoderm specific transcript protein
  • transcriptional intermediary factor 1
  • Chromobox Protein Homolog 5