The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression.

@article{citeulike:691356, abstract = {To investigate the determinants of promoter-specific gene regulation by the glucocorticoid receptor (GR), we compared the composition and function of regulatory complexes at two NFkappaB-responsive genes that are differentially regulated by GR. Transcription of the IL-8 and IkappaBalpha genes is stimulated by TNFalpha in A549 cells, but GR selectively represses IL-8 mRNA synthesis by inhibiting Ser2 phosphorylation of the RNA polymerase II (pol II) C-terminal domain (CTD). The proximal kappaB elements at these genes differ in sequence by a single base pair, and both recruited RelA and p50. Surprisingly, GR was recruited to both of these elements, despite the fact that GR failed to repress the IkappaBalpha promoter. Rather, the regulatory complexes formed at IL-8 and IkappaBalpha were distinguished by differential recruitment of the Ser2 CTD kinase, P-TEFb. Disruption of P-TEFb function by the Cdk-inhibitor, DRB, or by small interfering RNA selectively blocked TNFalpha stimulation of IL-8 mRNA production. GR competed with P-TEFb recruitment to the IL-8 promoter. Strikingly, IL-8 mRNA synthesis was repressed by GR at a post-initiation step, demonstrating that promoter proximal regulatory sequences assemble complexes that impact early and late stages of mRNA synthesis. Thus, GR accomplishes selective repression by targeting promoter-specific components of NFkappaB regulatory complexes.}, address = {Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA 94107-2280, USA.}, author = {Luecke, H. F. and Yamamoto, K. R. }, citeulike-article-id = {691356}, doi = {http://dx.doi.org/10.1101/gad.1297105}, issn = {0890-9369}, journal = {Genes Dev}, keywords = {cdk9, ctd-kinase, cyct, elongation, glucocorticoid, nfkappab, p-tefb, receptor, repression, transcription}, month = {May}, number = {9}, pages = {1116--1127}, posted-at = {2006-06-09 19:49:42}, priority = {4}, title = {The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression.}, url = {http://dx.doi.org/10.1101/gad.1297105}, volume = {19}, year = {2005} }

TY - JOUR ID - citeulike:691356 L3 - citeulike-article-id:691356 N2 - To investigate the determinants of promoter-specific gene regulation by the glucocorticoid receptor (GR), we compared the composition and function of regulatory complexes at two NFkappaB-responsive genes that are differentially regulated by GR. Transcription of the IL-8 and IkappaBalpha genes is stimulated by TNFalpha in A549 cells, but GR selectively represses IL-8 mRNA synthesis by inhibiting Ser2 phosphorylation of the RNA polymerase II (pol II) C-terminal domain (CTD). The proximal kappaB elements at these genes differ in sequence by a single base pair, and both recruited RelA and p50. Surprisingly, GR was recruited to both of these elements, despite the fact that GR failed to repress the IkappaBalpha promoter. Rather, the regulatory complexes formed at IL-8 and IkappaBalpha were distinguished by differential recruitment of the Ser2 CTD kinase, P-TEFb. Disruption of P-TEFb function by the Cdk-inhibitor, DRB, or by small interfering RNA selectively blocked TNFalpha stimulation of IL-8 mRNA production. GR competed with P-TEFb recruitment to the IL-8 promoter. Strikingly, IL-8 mRNA synthesis was repressed by GR at a post-initiation step, demonstrating that promoter proximal regulatory sequences assemble complexes that impact early and late stages of mRNA synthesis. Thus, GR accomplishes selective repression by targeting promoter-specific components of NFkappaB regulatory complexes. IS - 9 JF - Genes Dev SN - 0890-9369 AD - Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA 94107-2280, USA. EP - 1127 TI - The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression. VL - 19 SP - 1116 KW - cdk9 KW - ctd-kinase KW - cyct KW - elongation KW - glucocorticoid KW - nfkappab KW - p-tefb KW - receptor KW - repression KW - transcription AU - Luecke, HF AU - Yamamoto, KR PY - 2005/05/01/ UR - http://dx.doi.org/10.1101/gad.1297105 ER -