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Molecular and Cellular Biology, September 2003, p. 6455-6468, Vol. 23, No. 18
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.18.6455-6468.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Insulation of the Chicken ß-Globin Chromosomal Domain from a Chromatin-Condensing Protein, MENT

Department of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033,¹ W. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 117984,³ Department of Molecular Biology, M. V. Lomonosov Moscow State University, Moscow 119899, Russia,² Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111,⁴ Nuclear Reprogramming Laboratory, Division of Gene Expression and Development, The Roslin Institute (Edinburgh), Midlothian EH25 9PS, United Kingdom⁵

Received 2 April 2003/ Accepted 10 June 2003

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 ß-globin domain. We observed two sharp transitions of MENT concentration coinciding with the ß-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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