Histone Deacetylase 1 and 3 Regulate the Mesodermal Lineage Commitment of Mouse Embryonic Stem Cells

PLoS One

Guiying Wang¹  Jiuhong Kang¹  Weiying Lv¹  Xudong Guo¹  Yanxin Xu¹ 

[1] 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

关键词: Cell differentiation;    Mesoderm;    Gene expression;    Histones;    Gene regulation;    Transcription factors;    Ectoderm;    Endoderm;   

DOI  :  10.1371/journal.pone.0113262

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY