A multistep mechanism for the activation of rearrangement in the immune system

Yanhong Ji, Jianmin Zhang, Alfred Ian Lee, Howard Cedar, Yehudit Bergman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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 endogenous Κ locus in vivo. These results indicate that the regulation of rearrangement is carried out by a multilayered synergistic process.

Original languageAmerican English
Pages (from-to)7557-7562
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number13
DOIs
StatePublished - 24 Jun 2003

Fingerprint

Dive into the research topics of 'A multistep mechanism for the activation of rearrangement in the immune system'. Together they form a unique fingerprint.

Cite this