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

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.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

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.

Citovat

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.

@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.

Detailed Information on Publication Record