The role of histone chaperones in osteoblastic differentiation of C2C12 myoblasts.
Cellular differentiation is a process in which the cells gain a more specialized shape, metabolism, and function. These cellular changes are accompanied by dynamic changes in gene expression programs. In most cases, DNA methylation, histone modification, and variant histones drive the epigenetic transition that reprograms the gene expression. Histone chaperones, HIRA and Asf1a, have a role for cellular differentiation by deposition of one of variant histones, H3.3, during myogenesis of murine C2C12 cells. In this study, we accessed the roles of histone chaperones and histone H3.3 in osteoblastic conversion of C2C12 myoblasts and compared their roles with those for myogenic differentiation. The unbiased analysis of the expression pattern of histone chaperones and variant histones proposed their uncommon contribution to each pathway. HIRA and Asf1a decreased to ∼50% and further diminished during differentiation into osteoblasts, while they were maintained during differentiation into myotubes. HIRA, Asf1a, and H3.3 were indispensable for expression of cell type-specific genes during conversion into osteoblasts or myotubes. RNA interference analysis indicated that histone chaperones and H3.3 were required for early steps of osteoblastic differentiation. Our results suggest that histone chaperones and variant histones might be differentially required for the distinct phases of differentiation pathway.
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Tae-Yang
TY
Song
Jae-Hyun
JH
Yang
Jin Young
JY
Park
Yunkyoung
Y
Song
Jeung-Whan
JW
Han
Hong-Duk
HD
Youn
Eun-Jung
EJ
Cho
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D056488:Histone Chaperones / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000502:physiology; D051379:Mice; D018832:Molecular Chaperones; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
C547553:Asf1a protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C484187:Hira protein, mouse; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D017570:MyoD Protein; D018008:Myogenin; D034741:RNA, Small Interfering; D014157:Transcription Factors; D015675:Osteocalcin; D000469:Alkaline Phosphatase