OVEN, Irena, Nadezda BRDICKOVA, Jiří KOHOUTEK, Tomaž VAUPOTIČ, Mojca NARAT and B Matija PETERLIN. AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells. Molecular and Cellular Biology. Washington, D.C.: ASM, 2007, vol. 27, No 24, p. 8815-8823. ISSN 0270-7306. Available from: https://dx.doi.org/10.1128/MCB.04085-07.
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Basic information
Original name AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells
Authors OVEN, Irena, Nadezda BRDICKOVA, Jiří KOHOUTEK, Tomaž VAUPOTIČ, Mojca NARAT and B Matija PETERLIN.
Edition Molecular and Cellular Biology, Washington, D.C. ASM, 2007, 0270-7306.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 6.420
Doi http://dx.doi.org/10.1128/MCB.04085-07
UT WoS 000251527300034
Keywords in English AUTOIMMUNE REGULATOR PROTEIN; NUCLEAR RECEPTOR; BINDING PROTEIN; EXPRESSION; TOLERANCE; DOMAINS; HEXIM1; HIV-1; ACTIVATION; MUTATIONS
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Tags International impact, Reviewed
Changed by Changed by: Olga Křížová, učo 56639. Changed: 22/7/2012 07:44.
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 I genes. Indeed, by chromatin immunoprecipitation, we found that RNA polymerase 11 was already engaged on these promoters but was unable to elongate in the absence of AIRE. Moreover, the genetic inactivation of cyclin T1 from P-TEFb abolished the transcription of AIRE-responsive genes and led to lymphocytic infiltration of lacrimal and salivary glands in the CycT1(-/-) mouse. Our findings reveal critical steps by which AIRE regulates the transcription of genes that control central tolerance in the thymus.
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