Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promoters

KOHOUTEK, Jiří, Dalibor BLAŽEK and B Matija PETERLIN. Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promoters. Proceedings of the National Academy of Sciences of the United States of America. WASHINGTON: NATL ACAD SCIENCES, 2006, vol. 103, No 46, p. 17349-17354. ISSN 0027-8424. Available from: https://dx.doi.org/10.1073/pnas.0603079103.

Basic information

• Original name: Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promoters
• Authors: KOHOUTEK, Jiří, Dalibor BLAŽEK and B Matija PETERLIN.
• Edition: Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, NATL ACAD SCIENCES, 2006, 0027-8424.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 9.643
• Doi: http://dx.doi.org/10.1073/pnas.0603079103
• UT WoS: 000242249400052
• Keywords in English: RNA-POLYMERASE-II; MELANOMA CELL-LINES; P-TEFB; 7SK SNRNA; EXPRESSION; CIITA; COMPLEX; GENES; DIFFERENTIATION; ACTIVATION
• Tags: ok
• Tags: International impact, Reviewed

Abstract

The class II transactivator (CIITA) is the master integrator of expression of MHC class II genes. It interacts with variety of basal transcription factors to initiate and elongate transcription of these genes. Among others, it recruits positive transcription elongation factor b (P-TEFb) to MHC class II promoters. In cells, P-TEFb is found in small active or large inactive complexes. The large complex is composed of P-TEFb, 7SK small nuclear RNA, and hexamethylene bisacetamide-inducible protein 1 (Hexim1). The present study identifies Hexim1 as a potent inhibitor of CIITA-mediated transcription. Not only the exogenously expressed but also IFN-gamma-induced CIITA was inhibited by Hexim1. This inhibition did riot result from an association between Hexim1 and CIITA but depended on the intact Cyclin T1-binding domain in Hexim1. importantly, Hexim1 sequestered P-TEFb from CIITA, as documented by binding competition and ChIP assays. Conversely, the depletion of Hexim1 from cells by siRNA increased CIITA-mediated transcription. Thus, modulating ratios between active and inactive P-TEFb complexes is an additional mechanism of regulating transcriptional activators such as CIITA.