AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells.

ABSTRACT: AIRE is a transcriptional activator that directs the ectopic expression of many tissue-specific genes in medullary thymic epithelial cells, which plays an important role in the negative selection of autoreactive T cells. However, its mechanism of action remains poorly understood. In this study, we found that AIRE regulates the step of elongation rather than initiation of RNA polymerase II. For these effects, AIRE bound and recruited P-TEFb to target promoters in medullary thymic epithelial cells. In these cells, AIRE activated the ectopic transcription of insulin and salivary protein 1 genes. Indeed, by chromatin immunoprecipitation, we found that RNA polymerase II was already engaged on these promoters but was unable to elongate in the absence of AIRE. Moreover, the genetic inactivation o

SUBMITTER: Oven I 

PROVIDER: S-EPMC2169392 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature