Abstract
Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the positive transcription elongation factor b (P-TEFb). P-TEFb is composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK. The role of the C-terminal region of CycT1 and CycT2 remains unknown. In this report, we demonstrate that these sequences are essential for the activation of transcription by P-TEFb via DNA, i.e., when CycT1 is tethered upstream or downstream of promoters and coding sequences. A histidine-rich stretch, which is conserved between CycT1 and CycT2 in this region, bound the C-terminal domain of RNAPII. This binding was required for the subsequent expression of full-length transcripts from target genes. Thus, P-TEFb could mediate effects of enhancers on the elongation of transcription.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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Cyclin T
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Cyclin-Dependent Kinase 9
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Cyclin-Dependent Kinases / metabolism
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Cyclins / genetics
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Cyclins / metabolism
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DNA / metabolism
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Gene Expression Regulation*
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Gene Products, tat / metabolism
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Genes, Reporter
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HeLa Cells
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Humans
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Models, Genetic
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Positive Transcriptional Elongation Factor B
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Tertiary
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RNA Polymerase II / chemistry
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RNA Polymerase II / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Regulatory Sequences, Nucleic Acid / genetics
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Regulatory Sequences, Nucleic Acid / physiology*
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Transcription, Genetic*
Substances
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CCNT1 protein, human
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Cyclin T
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Cyclins
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Gene Products, tat
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Recombinant Fusion Proteins
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DNA
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Positive Transcriptional Elongation Factor B
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Protein Serine-Threonine Kinases
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CDK9 protein, human
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Cyclin-Dependent Kinase 9
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Cyclin-Dependent Kinases
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RNA Polymerase II