TY - JOUR
T1 - A multistep mechanism for the activation of rearrangement in the immune system
AU - Ji, Yanhong
AU - Zhang, Jianmin
AU - Lee, Alfred Ian
AU - Cedar, Howard
AU - Bergman, Yehudit
PY - 2003/6/24
Y1 - 2003/6/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038610946&partnerID=8YFLogxK
U2 - 10.1073/pnas.0932635100
DO - 10.1073/pnas.0932635100
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C2 - 12802019
AN - SCOPUS:0038610946
SN - 0027-8424
VL - 100
SP - 7557
EP - 7562
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -