Genome-wide analysis of histone H3 lysine9 modifications in human mesenchymal stem cell osteogenic differentiation

• Published in: PloS one Vol. 4; no. 8; p. e6792
• Main Authors: Tan, Jiang, Lu, Jun, Huang, Wei, Dong, Zhixiong, Kong, Chenfei, Li, Lin, Gao, Lina, Guo, Jianhua, Huang, Baiqu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2009; Public Library of Science (PLoS)
• Subjects: Alternations; Analysis; Biocompatibility; Bone and Bones - cytology; Cell cycle; Cell differentiation; Cell Differentiation - genetics; Cell self-renewal; Chromatin; Chromatin Immunoprecipitation; Cytoskeleton; Data processing; Developmental Biology/Cell Differentiation; Developmental Biology/Stem Cells; Differentiation (biology); DNA microarrays; Drosophila; Epigenetic inheritance; Epigenetics; Gene expression; Gene Expression Profiling; Genes; Genetics and Genomics/Epigenetics; Genome-Wide Association Study; Genomes; Genomics; Histone H3; Histones - chemistry; Histones - genetics; Humans; Lysine - genetics; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchyme; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Promoters; Reverse Transcriptase Polymerase Chain Reaction; Stem cells; Studies; Vitamin D
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006792

Mesenchymal stem cells (MSCs) possess self-renewal and multi-lineage differentiation potentials. It has been established that epigenetic mechanisms such as histone modifications could be critical for determining the fate of stem cells. In this study, full human genome promoter microarrays and expression microarrays were used to explore the roles of histone modifications (H3K9Ac and H3K9Me2) upon the induction of MSC osteogenic differentiation. Our results revealed that the enrichment of H3K9Ac was decreased globally at the gene promoters, whereas the number of promoters enriched with H3K9Me2 was increased evidently upon osteogenic induction. By a combined analysis of data from both ChIP-on-chip and expression microarrays, a number of differentially expressed genes regulated by H3K9Ac and/or H3K9Me2 were identified, implicating their roles in several biological events, such as cell cycle withdraw and cytoskeleton reconstruction that were essential to differentiation process. In addition, our results showed that the vitamin D receptor played a trans-repression role via alternations of H3K9Ac and H3K9Me2 upon MSC osteogenic differentiation. Data from this study suggested that gene activation and silencing controlled by changes of H3K9Ac and H3K9Me2, respectively, were crucial to MSC osteogenic differentiation.