title: Histone deacetylase 1 and 3 regulate the mesodermal lineage commitment of mouse embryonic stem cells.
abstract: The important role of histone acetylation alteration has become increasingly recognized in mesodermal lineage differentiation and development. However, the contribution of individual histone deacetylases (HDACs) to mesoderm specification remains poorly understood. In this report, we found that trichostatin A (TSA), an inhibitor of histone deacetylase (HDACi), could induce early differentiation of embryonic stem cells (ESCs) and promote mesodermal lineage differentiation. Further analysis showed that the expression levels of HDAC1 and 3 are decreased gradually during ESCs differentiation. Ectopic expression of HDAC1 or 3 significantly inhibited differentiation into the mesodermal lineage. By contrast, loss of either HDAC1 or 3 enhanced the mesodermal differentiation of ESCs. Additionally, we demonstrated that the activity of HDAC1 and 3 is indeed required for the regulation of mesoderm gene expression. Furthermore, HDAC1 and 3 were found to interact physically with the T-box transcription factor T/Bry, which is critical for mesodermal lineage commitment. These findings indicate a key mechanism for the specific role of HDAC1 and 3 in mammalian mesoderm specification.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Lv
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D005326:Fetal Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000201:enzymology* / Q000502:physiology; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein; D000099186:Histone Deacetylase 3
chemical_list: D005326:Fetal Proteins; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; D000099186:Histone Deacetylase 3; C012589:trichostatin A; C484389:Hdac1 protein, mouse