The small chromatin-binding protein p8 coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter
Autor: | Grace K. Pavlath, Amena Saleh, Ramkumar Sambasivan, Nagarekha Pasupuleti, Sirisha Cheedipudi, Jyotsna Dhawan |
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Rok vydání: | 2009 |
Předmět: |
Biology
MyoD Cell Line Myoblasts Mice eIF-2 Kinase MyoD Protein Animals Humans Growth Substances Muscle Skeletal Promoter Regions Genetic Myogenin Regulation of gene expression PITX2 Myogenesis Chromatin binding Cell Cycle Gene Expression Regulation Developmental Cell Differentiation Cell Biology musculoskeletal system Molecular biology Chromatin Neoplasm Proteins DNA-Binding Proteins E1A-Associated p300 Protein Protein Binding Research Article |
Zdroj: | Journal of Cell Science. 122:3481-3491 |
ISSN: | 1477-9137 0021-9533 |
DOI: | 10.1242/jcs.048678 |
Popis: | Quiescent muscle progenitors called satellite cells persist in adult skeletal muscle and, upon injury to muscle, re-enter the cell cycle and either undergo self-renewal or differentiate to regenerate lost myofibers. Using synchronized cultures of C2C12 myoblasts to model these divergent programs, we show that p8 (also known as Nupr1), a G1-induced gene, negatively regulates the cell cycle and promotes myogenic differentiation. p8 is a small chromatin protein related to the high mobility group (HMG) family of architectural factors and binds to histone acetyltransferase p300 (p300, also known as CBP). We confirm this interaction and show that p300-dependent events (Myc expression, global histone acetylation and post-translational acetylation of the myogenic regulator MyoD) are all affected in p8-knockdown myoblasts, correlating with repression of MyoD target-gene expression and severely defective differentiation. We report two new partners for p8 that support a role in muscle-specific gene regulation: p68 (Ddx5), an RNA helicase reported to bind both p300 and MyoD, and MyoD itself. We show that, similar to MyoD and p300, p8 and p68 are located at the myogenin promoter, and that knockdown of p8 compromises chromatin association of all four proteins. Thus, p8 represents a new node in a chromatin regulatory network that coordinates myogenic differentiation with cell-cycle exit. |
Databáze: | OpenAIRE |
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