Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence

Sergei A Grigoryev, Tatiana Nikitina, John R Pehrson, Prim B Singh, Christopher L Woodcock

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Quiescent lymphocytes have small nuclei, filled with masses of facultative heterochromatin. Upon receiving mitogenic signals, these cells undergo nuclear enlargement, chromatin decondensation, the reactivation of cell proliferation, and changes in the intranuclear positioning of key genes. We examined the levels and intranuclear localization of major histone modifications and non-histone heterochromatin proteins in quiescent and reactivated mouse spleen lymphocytes. Dramatic and selective changes in localization of two heterochromatin-associated proteins, the histone variant macroH2A and HP1alpha occurred during lymphocyte reactivation. Reciprocal changes in the locations of these two proteins were observed in activated lymphocytes and cultured mouse fibroblasts induced into quiescence. We also describe a new apocentric nuclear compartment with a unique set of histone modifications that occurs as a zone of chromatin surrounding centromeric heterochromatin in differentiated lymphocytes. It is within this zone that the most significant changes occur in the transition from proliferation to quiescence. Our results suggest that constitutive centromeric heterochromatin plays an active role in cell differentiation and reactivation.

Original languageEnglish
Pages (from-to)6153-62
Number of pages10
JournalJournal of Cell Science
Volume117
Issue numberPt 25
DOIs
Publication statusPublished - Dec 1 2004

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Heterochromatin
Epigenomics
Chromatin
Lymphocytes
Histone Code
Proteins
Cell Differentiation
Spleen
Fibroblasts
Cell Proliferation
Genes

Keywords

  • 3T3 Cells
  • Animals
  • Blotting, Western
  • Bromodeoxyuridine
  • Cell Differentiation
  • Cell Nucleus
  • Cell Proliferation
  • Centromere
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Coloring Agents
  • Fibroblasts
  • Heterochromatin
  • Histones
  • Image Processing, Computer-Assisted
  • Lymphocyte Activation
  • Lymphocytes
  • Mice
  • Plasmids
  • Spleen
  • Transfection
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

Cite this

Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence. / Grigoryev, Sergei A; Nikitina, Tatiana; Pehrson, John R; Singh, Prim B; Woodcock, Christopher L.

In: Journal of Cell Science, Vol. 117, No. Pt 25, 01.12.2004, p. 6153-62.

Research output: Contribution to journalArticle

Grigoryev, Sergei A ; Nikitina, Tatiana ; Pehrson, John R ; Singh, Prim B ; Woodcock, Christopher L. / Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence. In: Journal of Cell Science. 2004 ; Vol. 117, No. Pt 25. pp. 6153-62.
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AU - Woodcock, Christopher L

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AB - Quiescent lymphocytes have small nuclei, filled with masses of facultative heterochromatin. Upon receiving mitogenic signals, these cells undergo nuclear enlargement, chromatin decondensation, the reactivation of cell proliferation, and changes in the intranuclear positioning of key genes. We examined the levels and intranuclear localization of major histone modifications and non-histone heterochromatin proteins in quiescent and reactivated mouse spleen lymphocytes. Dramatic and selective changes in localization of two heterochromatin-associated proteins, the histone variant macroH2A and HP1alpha occurred during lymphocyte reactivation. Reciprocal changes in the locations of these two proteins were observed in activated lymphocytes and cultured mouse fibroblasts induced into quiescence. We also describe a new apocentric nuclear compartment with a unique set of histone modifications that occurs as a zone of chromatin surrounding centromeric heterochromatin in differentiated lymphocytes. It is within this zone that the most significant changes occur in the transition from proliferation to quiescence. Our results suggest that constitutive centromeric heterochromatin plays an active role in cell differentiation and reactivation.

KW - 3T3 Cells

KW - Animals

KW - Blotting, Western

KW - Bromodeoxyuridine

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KW - Cell Proliferation

KW - Centromere

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