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@article{987488, author = {Oven, Irena and Brdickova, Nadezda and Kohoutek, Jiří and Vaupotič, Tomaž and Narat, Mojca and Peterlin, B Matija}, article_location = {Washington, D.C.}, article_number = {24}, doi = {http://dx.doi.org/10.1128/MCB.04085-07}, keywords = {AUTOIMMUNE REGULATOR PROTEIN; NUCLEAR RECEPTOR; BINDING PROTEIN; EXPRESSION; TOLERANCE; DOMAINS; HEXIM1; HIV-1; ACTIVATION; MUTATIONS}, language = {eng}, issn = {0270-7306}, journal = {Molecular and Cellular Biology}, title = {AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells}, url = {http://mcb.asm.org/content/27/24/8815.full}, volume = {27}, year = {2007} }
TY - JOUR ID - 987488 AU - Oven, Irena - Brdickova, Nadezda - Kohoutek, Jiří - Vaupotič, Tomaž - Narat, Mojca - Peterlin, B Matija PY - 2007 TI - AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells JF - Molecular and Cellular Biology VL - 27 IS - 24 SP - 8815-8823 EP - 8815-8823 PB - ASM SN - 02707306 KW - AUTOIMMUNE REGULATOR PROTEIN KW - NUCLEAR RECEPTOR KW - BINDING PROTEIN KW - EXPRESSION KW - TOLERANCE KW - DOMAINS KW - HEXIM1 KW - HIV-1 KW - ACTIVATION KW - MUTATIONS UR - http://mcb.asm.org/content/27/24/8815.full N2 - 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. ER -
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. \textit{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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