期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 13, 页码 7557-7562出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0932635100
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Rearrangement of immune receptor loci is a developmentally controlled process that takes place exclusively in lymphoid cells. We have used a stable transfection system in pre-B cells to show that DNA methylation brings about histone underacetylation, histone H3(K9) methylation, DNasel resistance, and strong inhibition of both transcription and recombination. Strikingly, this repression is maintained in dividing cells even after removal of the original methyl groups responsible for its establishment, but in this state, rearrangement can now be induced by reacetylation of local histones using the drug Trichostatin A. This same combination of demethylation and histone acetylation is also required to activate germline transcription and recombination from the endogeneous kappa locus in vivo. These results indicate that the regulation of rearrangement is carried out by a multilayered synergistic process.
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