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

26 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

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beta-Globins
Histones
Chromatin
Chickens
Insulator Elements
Proteins
Lysine
NIH 3T3 Cells
Chromatin Assembly and Disassembly
Histone Code
Genes
Trypsin
Erythrocytes
Peptides

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.

Cite this

Istomina, N. E., Shushanov, S. S., Springhetti, E. M., Karpov, V. L., Krasheninnikov, I. A., Stevens, K., ... 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.

Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT. / Istomina, Natalia E; Shushanov, Sain S; Springhetti, Evelyn M; Karpov, Vadim L; Krasheninnikov, Igor A; Stevens, Kimberly; Zaret, Kenneth S; Singh, Prim B; Grigoryev, Sergei A.

In: Molecular and Cellular Biology, Vol. 23, No. 18, 09.2003, p. 6455-68.

Research output: Contribution to journalArticle

Istomina, NE, Shushanov, SS, Springhetti, EM, Karpov, VL, Krasheninnikov, IA, Stevens, K, Zaret, KS, Singh, PB & Grigoryev, SA 2003, 'Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT', Molecular and Cellular Biology, vol. 23, no. 18, pp. 6455-68.
Istomina NE, Shushanov SS, Springhetti EM, Karpov VL, Krasheninnikov IA, Stevens K et al. Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT. Molecular and Cellular Biology. 2003 Sep;23(18):6455-68.
Istomina, Natalia E ; Shushanov, Sain S ; Springhetti, Evelyn M ; Karpov, Vadim L ; Krasheninnikov, Igor A ; Stevens, Kimberly ; Zaret, Kenneth S ; Singh, Prim B ; Grigoryev, Sergei A. / Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 18. pp. 6455-68.
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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.",
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AU - Istomina, Natalia E

AU - Shushanov, Sain S

AU - Springhetti, Evelyn M

AU - Karpov, Vadim L

AU - Krasheninnikov, Igor A

AU - Stevens, Kimberly

AU - Zaret, Kenneth S

AU - Singh, Prim B

AU - Grigoryev, Sergei A

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N2 - 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.

AB - 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.

KW - 3T3 Cells

KW - Acetylation

KW - Animals

KW - Avian Proteins

KW - Cell Division

KW - Cells, Cultured

KW - Chickens

KW - Chromatin

KW - Chromosomal Proteins, Non-Histone

KW - Enzyme Inhibitors

KW - Erythrocytes

KW - Globins

KW - Histone Deacetylase Inhibitors

KW - Histones

KW - Lymphocytes

KW - Lysine

KW - Methylation

KW - Mice

KW - Protein Structure, Tertiary

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

M3 - Article

VL - 23

SP - 6455

EP - 6468

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 18

ER -