Epigenetic regulation in chondrogenesis.
Epigenetics is an essential mechanism to control gene expression and fundamental cellular processes. DNA methylation in CpG-rich promoters correlates with gene silencing. Histone modification including histone acetylation and deacetylation determines the stability of the chromatin structure. Condensed chromatin (heterochromatin), which has a higher-order histone-DNA structure, prevents the access of transcriptional activators to their target genes. The fundamental unit of eukaryotic chromatin consists of 146 bp of DNA wrapped around a histone octamer. Posttranslational modifications of the histone tail and the chromatin remodeling complex disrupt histone-DNA contacts and induce nucleosome mobilization. Histone acetylation of specific lysine residues in the histone tail plays a crucial role in epigenetic regulation. Histone acetylation is a dynamic process regulated by the antagonistic actions of 2 families of enzymes - the histone acetyltransferases (HATs) and the histone deacetylases (HDACs). The balance between histone acetylation and deacetylation serves as a key epigenetic mechanism for transcription factor-dependent gene expression and the developmental process. We review emerging evidence that DNA methylation, histone acetylation modified by HAT and/or HDAC, and transcription factor-associated molecules contribute to a mechanism that can alter chromatin structure, gene expression, and cellular differentiation during chondrogenesis.
Furumatsu
Takayuki
T
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Detistry and Pharmaceucial Sciences, Okayama 700-8558, Japan. matino@md.okayama-u.ac.jp
Ozaki
Toshifumi
T
D000107:Acetylation; D000818:Animals; D020219:Chondrogenesis / Q000235:genetics* / Q000502:physiology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins
D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins