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

55 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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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.

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