Identification of a novel function for the chromatin remodeling protein ING2 in muscle differentiation

• Published in: PloS one 2012-07, Vol.7 (7), p.e40684
• Main Authors: Eapen, Shawn A, Netherton, Stuart J, Sarker, Krishna P, Deng, Lili, Chan, Angela, Riabowol, Karl, Bonni, Shirin
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino acids; Analysis; Animals; Apoptosis; Binding Sites; Biochemistry; Biology; Cancer; Cell cycle; Cell death; Cell Differentiation; Cell growth; Cell proliferation; Chromatin; Chromatin Assembly and Disassembly; Chromatin remodeling; Differentiation (biology); Discosoma; DNA binding proteins; Epigenetic inheritance; Epigenetics; Gene expression; Gene Knockdown Techniques; Growth factors; Histones - metabolism; Homeobox; Homeodomain Proteins - chemistry; Homeodomain Proteins - metabolism; Humans; Leucine; Leucine zipper proteins; Leucine Zippers; Lysine - metabolism; Medical research; Medicine; Methylation; Mice; Molecular biology; Muscle Cells - cytology; Muscle Cells - metabolism; Muscle Development; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Myoblasts - cytology; Myoblasts - metabolism; Myogenesis; Myotubes; Oncology; Phase transitions; Protein Binding; Protein Structure, Tertiary; Proteins; Ribonucleic acid; RNA; RNA-mediated interference; Structure-function relationships; Tumor suppression; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - metabolism; Tumors; Zinc; Zinc finger proteins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040684

The inhibitor of growth (ING) family of zinc-finger plant homeodomain (PHD)-containing chromatin remodeling protein controls gene expression and has been implicated in the regulation of cell proliferation and death. However, the role of ING proteins in cell differentiation remains largely unexplored. Here, we identify an essential function for ING2 in muscle differentiation. We find that knockdown of ING2 by RNA interference (RNAi) blocks the differentiation of C2C12 cells into myotubes, suggesting that ING2 regulates the myogenic differentiation program. We also characterize a mechanism by which ING2 drives muscle differentiation. In structure-function analyses, we find that the leucine zipper motif of ING2 contributes to ING2-dependent muscle differentiation. By contrast, the PHD domain, which recognizes the histone H3K4me3 epigenetic mark, inhibits the ability of ING2 to induce muscle differentiation. We also find that the Sin3A-HDAC1 chromatin remodeling complex, which interacts with ING2, plays a critical role in ING2-dependent muscle differentiation. These findings define a novel function for ING2 in muscle differentiation and bear significant implications for our understanding of the role of the ING protein family in cell differentiation and tumor suppression.