The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.

The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyte enhancer factor 2 (MEF2) family of transcription factors, key regulatory factors for myocyte development. Knockdown of endogenous cyclin T1 in murine C2C12 cells abolishes MEF2-dependent reporter gene expression as well as transcription of endogenous MEF2 target genes, whereas overexpression of P-TEFb enhances MEF2-dependent transcription. P-TEFb interacts with MEF2 both in vitro and in vivo. Activation of MEF2-dependent transcription induced by serum starvation is mediated by a rapid dissociation of P-TEFb from its inhibitory subunit, HEXIM1, and a subsequent recruitment of P-TEFb to MEF2 binding sites in the promoter region of MEF2 target genes. These results indicate that recruitment of P-TEFb is a critical step for stimulation of MEF2-dependent transcription, therefore providing a fundamentally important regulatory mechanism underlying the transcriptional program in muscle cells.
AuthorsMasanori Nojima, Yehong Huang, Mudit Tyagi, Hung-Ying Kao, Koh Fujinaga
JournalJournal of molecular biology (J Mol Biol) Vol. 382 Issue 2 Pg. 275-87 (Oct 03 2008) ISSN: 1089-8638 [Electronic] Netherlands
PMID18662700 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • CCNT1 protein, human
  • Cyclin T
  • Cyclins
  • DNA-Binding Proteins
  • Glucose Transporter Type 4
  • Hexim1 protein, mouse
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • NR4A1 protein, human
  • Nr4a1 protein, mouse
  • Nr4a1 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Receptors, Steroid
  • Transcription Factors
  • Positive Transcriptional Elongation Factor B
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
  • JNK Mitogen-Activated Protein Kinases
  • Animals
  • Cells, Cultured
  • Cyclin T
  • Cyclin-Dependent Kinase 9 (genetics, metabolism)
  • Cyclins (genetics, metabolism)
  • DNA-Binding Proteins (genetics, metabolism)
  • Gene Expression Regulation
  • Genes, Reporter
  • Glucose Transporter Type 4 (genetics, metabolism)
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
  • MEF2 Transcription Factors
  • Mice
  • Muscle Cells (cytology, physiology)
  • Muscle, Skeletal (cytology)
  • Myogenic Regulatory Factors (genetics, metabolism)
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Positive Transcriptional Elongation Factor B (genetics, metabolism)
  • Promoter Regions, Genetic
  • RNA, Small Interfering (genetics, metabolism)
  • RNA-Binding Proteins
  • Rats
  • Receptors, Steroid (genetics, metabolism)
  • Transcription Factors (genetics, metabolism)
  • Transcription, Genetic

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