Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT

Natalia E Istomina, Sain S Shushanov, Evelyn M Springhetti, Vadim L Karpov, Igor A Krasheninnikov, Kimberly Stevens, Kenneth S Zaret, Prim B Singh, Sergei A Grigoryev

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Active genes are insulated from developmentally regulated chromatin condensation in terminally differentiated cells. We mapped the topography of a terminal stage-specific chromatin-condensing protein, MENT, across the active chicken beta-globin domain. We observed two sharp transitions of MENT concentration coinciding with the beta-globin boundary elements. The MENT distribution profile was opposite to that of acetylated core histones but correlated with that of histone H3 dimethylated at lysine 9 (H3me2K9). Ectopic MENT expression in NIH 3T3 cells caused a large-scale and specific remodeling of chromatin marked by H3me2K9. MENT colocalized with H3me2K9 both in chicken erythrocytes and NIH 3T3 cells. Mutational analysis of MENT and experiments with deacetylase inhibitors revealed the essential role of the reaction center loop domain and an inhibitory affect of histone hyperacetylation on the MENT-induced chromatin remodeling in vivo. In vitro, the elimination of the histone H3 N-terminal peptide containing lysine 9 by trypsin blocked chromatin self-association by MENT, while reconstitution with dimethylated but not acetylated N-terminal domain of histone H3 specifically restored chromatin self-association by MENT. We suggest that histone H3 modification at lysine 9 directly regulates chromatin condensation by recruiting MENT to chromatin in a fashion that is spatially constrained from active genes by gene boundary elements and histone hyperacetylation.

Original languageEnglish
Pages (from-to)6455-68
Number of pages14
JournalMolecular and Cellular Biology
Volume23
Issue number18
Publication statusPublished - Sep 2003

Keywords

  • 3T3 Cells
  • Acetylation
  • Animals
  • Avian Proteins
  • Cell Division
  • Cells, Cultured
  • Chickens
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Enzyme Inhibitors
  • Erythrocytes
  • Globins
  • Histone Deacetylase Inhibitors
  • Histones
  • Lymphocytes
  • Lysine
  • Methylation
  • Mice
  • Protein Structure, Tertiary
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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  • Cite this

    Istomina, N. E., Shushanov, S. S., Springhetti, E. M., Karpov, V. L., Krasheninnikov, I. A., Stevens, K., Zaret, K. S., Singh, P. B., & Grigoryev, S. A. (2003). Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT. Molecular and Cellular Biology, 23(18), 6455-68.