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Controlling the Elongation Phase of Transcription with P-TEFb

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1 Controlling the Elongation Phase of Transcription with P-TEFb
B. Matija Peterlin, David H. Price  Molecular Cell  Volume 23, Issue 3, Pages (August 2006) DOI: /j.molcel Copyright © 2006 Elsevier Inc. Terms and Conditions

2 Figure 1 Steps of Transcription by RNAPII
Four stages of transcription are depicted: (1) preinitiation complex (PIC) formation, (2) promoter clearance with the phoshorylation of serines at position 5 of the CTD, (3) recruitment of human capping enzymes (HCE), 5′ capping (m7G) of nascent transcripts, and pausing of RNAPII, and (4) recruitment of P-TEFb with the phosphorylation of serines at position 2 in the CTD, followed by productive elongation and cotranscriptional processing by splicing (SR) and polyadenylation (pA) machineries. Phosphorylated serines at positions 2 and 5 in the heptapeptide repeats of the CTD of the large subunit of RNAPII are depicted by white letters in red circles. Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2006 Elsevier Inc. Terms and Conditions

3 Figure 2 Recruitment of P-TEFb to Transcription Complexes
Depicted are five mechanisms responsible for the recruitment of P-TEFb to genes: (1) artificial tethering (Gal4 DNA binding domain fusions), (2) coactivator (CIITA), (3) DNA bound activator (NF-κB, c-Myc, and nuclear receptors), (4) RNA bound activator (HIV Tat), and (5) chromatin bound activator (Brd4). Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2006 Elsevier Inc. Terms and Conditions

4 Figure 3 Active Repression of P-TEFb
The left panel of the diagram depicts the typical activation of transcriptional elongation by P-TEFb, where CycT1 mediates interactions with the CTD of RNAPII. The panel on the right demonstrates how a repressor can block this activation by binding CycT1 and preventing the subsequent phosphorylation of RNAPII, DSIF, and NELF. Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2006 Elsevier Inc. Terms and Conditions

5 Figure 4 Active and Inactive Complexes of P-TEFb
P-TEFb is regulated by its reversible association with HEXIM1 and HEXIM2 and 7SK snRNA. Binding of a HEXIM dimer to 7SK snRNA causes a conformational change that unmasks P-TEFb binding domains on these proteins. Moreover, when P-TEFb is in this RNA-protein complex, its kinase activity is inhibited. Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2006 Elsevier Inc. Terms and Conditions

6 Figure 5 Phylogenetic Analyses of Elongation Control Factors
Sequences from the indicated proteins in the species listed were compared to human sequences. Fish, D. rerio; fly, D. melanogaster; sea urchin, S. purpuratus; worm, C. elegans; budding yeast, S. cerevisiae; and fission yeast, S. pombe. The number of identical and highly similar residues was determined using ClustalW , and the results are expressed as a percent similarity with the total residues in the human factor. For 7SK snRNA, only identical nucleotides were used. Abbreviations: NF, not found; F, found, but not enough sequence for complete alignment. In some species, only one ortholog exists although there are two in humans. Pairs of values written off the center indicate there is only one ortholog, and the two numbers represent comparisons to each of the two human proteins. Cdk9 for the two yeasts are Bur1/Ctk1. Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2006 Elsevier Inc. Terms and Conditions


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