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.