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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Line
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Cell Lineage*
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Fetal Proteins / metabolism*
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Gene Expression Regulation
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Histone Deacetylase 1 / genetics
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Histone Deacetylase 1 / metabolism*
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Histone Deacetylase Inhibitors / pharmacology
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Hydroxamic Acids / pharmacology
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Mesoderm / physiology*
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Mice
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Mouse Embryonic Stem Cells / enzymology*
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Mouse Embryonic Stem Cells / physiology
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T-Box Domain Proteins / metabolism*
Substances
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Fetal Proteins
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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T-Box Domain Proteins
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trichostatin A
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Hdac1 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylases
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histone deacetylase 3
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Brachyury protein
Grants and funding
This work was supported by grants obtained from the Ministry of Science and Technology (grant numbers 2011CB965100, 2010CB944900, 2011CBA01100, 2012CB966603, 2013CB967600, 2013CB967401), National Natural Science Foundation of China (grant numbers 91219305, 31210103905, 31371510, 31101061, 31171432, 81170499, 31201107, 31301208, 81201599), Science and Technology Commission of Shanghai Municipality (grant number 12ZR1450900), IRT1168 from Ministry of Education, sponsored by Shanghai Rising-Star Program (14QA1403900), Specialized Research Fund for the Doctoral Program of Higher Education (20110072110039), support of the “Chen Guang” project from the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (12CG19) and the Fundamental Research Funds for the Central Universities (2000219099). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.