Inhibition of histone deacetylases alters allelic chromatin conformation at the imprinted U2af1-rs1 locus in mouse embryonic stem cells

J Biol Chem. 2002 Apr 5;277(14):11728-34. doi: 10.1074/jbc.M105775200. Epub 2002 Jan 30.


Most loci that are regulated by genomic imprinting have differentially methylated regions (DMRs). Previously, we showed that the DMRs of the mouse Snrpn and U2af1-rs1 genes have paternal allele-specific patterns of acetylation on histones H3 and H4. To investigate the maintenance of acetylation at these DMRs, we performed chromatin immunoprecipitation on trichostatin-A (TSA)-treated and control cells. In embryonic stem (ES) cells and fibroblasts, brief (6-h) TSA treatment induces global hyperacetylation of H3 and H4. In ES cells only, TSA led to a selective increase in maternal acetylation at U2af1-rs1, at lysine 5 of H4 and at lysine 14 of H3. TSA treatment of ES cells did not affect DNA methylation or expression of U2af1-rs1, but was sufficient to increase DNase I sensitivity along the maternal allele to a level comparable with that of the paternal allele. In fibroblasts, TSA did not alter U2af1-rs1 acetylation, and the parental alleles retained their differential DNase I sensitivity. At Snrpn, no changes in acetylation were observed in the TSA-treated cells. Our data suggest that the mechanisms regulating histone acetylation at DMRs are locus and developmental stage-specific and are distinct from those effecting global levels of acetylation. Furthermore, it seems that the allelic U2af1-rs1 acetylation determines DNase I sensitivity/chromatin conformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Alleles
  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • DNA Methylation
  • Deoxyribonuclease I / metabolism
  • Deoxyribonucleases / metabolism
  • Embryo, Mammalian / cytology*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Fibroblasts / metabolism
  • Genomic Imprinting*
  • Histone Deacetylase Inhibitors*
  • Histones / metabolism
  • Hydroxamic Acids / pharmacology
  • Kidney / metabolism
  • Lysine / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Nuclear Proteins*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Precipitin Tests
  • Protein Conformation
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleoproteins*
  • Splicing Factor U2AF
  • Stem Cells / metabolism*
  • Time Factors
  • Tissue Distribution


  • Chromatin
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteins
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • Zrsr1 protein, mouse
  • trichostatin A
  • Deoxyribonucleases
  • Deoxyribonuclease I
  • Lysine

Associated data

  • GENBANK/AF309654