Controlling the Elongation Phase of Transcription with P-TEFb

ArticleinMolecular Cell 23(3):297-305 · September 2006with18 Reads
DOI: 10.1016/j.molcel.2006.06.014 · Source: PubMed
The positive transcription elongation factor b (P-TEFb) is a cyclin-dependent kinase that controls the elongation phase of transcription by RNA polymerase II (RNAPII). This process is made possible by the reversal of effects of negative elongation factors that include NELF and DSIF. In complex organisms, elongation control is critical for the regulated expression of most genes. In those organisms, the function of P-TEFb is influenced negatively by HEXIM proteins and 7SK snRNA and positively by a variety of recruiting factors. Phylogenetic analyses of the components of the human elongation control machinery indicate that the number of mechanisms utilized to regulate P-TEFb function increased as organisms developed more complex developmental patterns.
    • "In recent years, however, an alternative picture has emerged whereby early transcription elongation represents a critical rate-limiting step for up to 40% of regulated genes [59, 60]. At such genes, Pol II initiates transcription prior to stimulation but pauses ~50 nucleotides from the TSS bound by the Negative Elongation Factor (NELF) [59][60][61][62]. Upon exposure to relevant stimulus, positive transcription elongation factor P-TEFb, composed of cyclin T1 and CDK9, phosphorylates "
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    • "RNAPII enters the PIC hypo-phosphorylated. During initiation, the CTD is phosphorylated on Ser5 primarily by CDK7 (Spangler et al., 2001; Tirode et al., 1999), and subsequently on Ser2 by BRD4 (Devaiah et al., 2012; Wu and Chiang, 2007), PTEF-b (Peterlin and Price, 2006 ), and other kinases during pauserelease and elongation (Kwak and Lis, 2013). Therefore, we asked whether RNAPII phosphorylation affected TOP1 activity. "
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