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Regulation of transcript elongation through cooperative and ordered recruitment of cofactors Export

J. Biol. Chem. (29 May 2007), M701420200.

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cofactor cofactors cooperative elongation mrna recruitment rnapii transcript

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We studied the regulation of murine CD80, a gene whose basal transcriptional status was characterized by the presence of a stalled RNA polymerase II complex on the promoter-proximal region. Stimulus-induced activation of productive elongation involved a complex interplay of regulated events that included a synergy between ordered co-factor recruitment. This cascade of recruitments was initiated through the engagement of transcription factor NF-[kappa]B, leading to the temporal association of histone acetyltransferases and the consequent selective acetylation of a transcription start site-downstream nucleosome. This in turn culminated into the nucleosomal association of Brd4-associated P-TEFb, a protein complex containing kinase specific for serine 2 of Rbp 1, the largest subunit of carboxyl terminal domain (CTD) of RNA polymerase II. The consequent phosphorylation of serine 2 residues in CTD by CDK9 in P-TEFb complex then facilitated escape of polymerase II into the productive elongation phase. Thus, the cooperative mechanisms that integrate between independent pathways characterize regulation of the elongation step of transcription; thereby providing another level at which specificity of gene regulation can be achieved. 10.1074/jbc.M701420200


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