J 2007

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

OVEN, Irena, Nadezda BRDICKOVA, Jiří KOHOUTEK, Tomaž VAUPOTIČ, Mojca NARAT et. al.

Základní údaje

Originální název

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

Autoři

OVEN, Irena, Nadezda BRDICKOVA, Jiří KOHOUTEK, Tomaž VAUPOTIČ, Mojca NARAT a B Matija PETERLIN

Vydání

Molecular and Cellular Biology, Washington, D.C. ASM, 2007, 0270-7306

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 6.420

UT WoS

000251527300034

Klíčová slova anglicky

AUTOIMMUNE REGULATOR PROTEIN; NUCLEAR RECEPTOR; BINDING PROTEIN; EXPRESSION; TOLERANCE; DOMAINS; HEXIM1; HIV-1; ACTIVATION; MUTATIONS

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 22. 7. 2012 07:44, Olga Křížová

Anotace

V originále

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.