
The small chromatin-binding protein p8 coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter
Author(s) -
Ramkumar Sambasivan,
Sirisha Cheedipudi,
Nagarekha Pasupuleti,
Amena Saleh,
Grace K. Pavlath,
Jyotsna Dhawan
Publication year - 2009
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.048678
Subject(s) - myogenin , myod , biology , myod protein , chromatin , c2c12 , myogenesis , myogenic regulatory factors , microbiology and biotechnology , myocyte , histone , myf5 , chromatin immunoprecipitation , promoter , gene expression , genetics , gene
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.