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Cardiac Lineage Protein‐1 (CLP‐1) regulates the skeletal myogenic program through its association with MyoD and histone deacetylases (HDACs)
Author(s) -
Galatioto Josephine,
Mascareno Eduardo,
Siddiqui M.A.Q.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.825.1
Subject(s) - myod , myogenesis , p tefb , biology , microbiology and biotechnology , skeletal muscle , histone , rna polymerase ii , c2c12 , gene , myocyte , gene expression , genetics , promoter , endocrinology
Transcription in eukaryotic cells is regulated by the positive transcription elongation complex b (P‐TEFb), which appears to be dynamically partitioned between the active versus inactive states. In its active form, P‐TEFb contains cyclin T1 or T2 and cdk9 kinase which phosphorylates the CTD of RNA polymerase II resulting in elongation of the nascent transcripts to full‐length mRNAs. P‐TEFb in the inactive form contains the inhibitory protein CLP‐1/HEXIM1 and 7SK snRNA. CLP‐1 (Cardiac Lineage Protein‐1), the mouse ortholog of human HEXIM1, was cloned and the gene for CLP‐1 was knocked out in mice in our laboratory. In this study, we have begun to examine the role of CLP‐1 in skeletal muscle differentiation using the mouse C2C12 skeletal muscle cell line. We observed that CLP‐1 participates with both MyoD and HDACs which mediate P‐TEFb function. To further understand the role of CLP‐1 protein, we produced CLP‐1 overexpressing and CLP‐1 +/− C2C12 cells. Overexpression of CLP‐1 did not induce any prominent phenotype. On the other hand CLP‐1‐deficient cells were unable to differentiate into myotubes. Taken together, these data suggest that CLP‐1 plays a critical role in the genetic differentiation program of skeletal muscle cells. Supported by a grant from the National Institutes of Health (HL 07339‐M.A.Q. Siddiqui)