Distinct patterns of histone modifications at cardiac-specific gene promoters between cardiac stem cells and mesenchymal stem cells

Meijing Wang, Qing Yu, Lina Wang, Hongmei Gu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic capacity of MSCs and CSCs remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell fate commitment. Here we hypothesize that specific histone modifications accompany cardiac-specific gene expression, thus determining the differentiation capacity of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of gene activation, were higher in CSCs (Sca-1+CD29+) than MSCs. Additionally, lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led to increased cardiac gene expression and was accompanied by enhanced acH3 and acH4 levels at gene loci. We conclude that greater levels of histone acetylation at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for CSCs to develop into cardiomyocytes. These lineage-differential histone modifications are likely due to less HDAC recruitment at cardiac-specific gene promoters in CSCs than MSCs.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume304
Issue number11
DOIs
StatePublished - Jun 1 2013

Fingerprint

Histone Code
Mesenchymal Stromal Cells
Stem Cells
Genes
Acetylation
Histones
Gene Expression
Cardiac Myocytes
Genetic Promoter Regions
trichostatin A
Histone Deacetylase 1
Histone Deacetylase Inhibitors
Histone Deacetylases
Small Interfering RNA
Transcriptional Activation

Keywords

  • Cardiomyogenesis
  • Epigenetic regulation
  • Stem cell

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

@article{be882e24c8bd4bdd98bd3591c73d70ae,
title = "Distinct patterns of histone modifications at cardiac-specific gene promoters between cardiac stem cells and mesenchymal stem cells",
abstract = "Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic capacity of MSCs and CSCs remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell fate commitment. Here we hypothesize that specific histone modifications accompany cardiac-specific gene expression, thus determining the differentiation capacity of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of gene activation, were higher in CSCs (Sca-1+CD29+) than MSCs. Additionally, lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led to increased cardiac gene expression and was accompanied by enhanced acH3 and acH4 levels at gene loci. We conclude that greater levels of histone acetylation at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for CSCs to develop into cardiomyocytes. These lineage-differential histone modifications are likely due to less HDAC recruitment at cardiac-specific gene promoters in CSCs than MSCs.",
keywords = "Cardiomyogenesis, Epigenetic regulation, Stem cell",
author = "Meijing Wang and Qing Yu and Lina Wang and Hongmei Gu",
year = "2013",
month = "6",
day = "1",
doi = "10.1152/ajpcell.00359.2012",
language = "English",
volume = "304",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "11",

}

TY - JOUR

T1 - Distinct patterns of histone modifications at cardiac-specific gene promoters between cardiac stem cells and mesenchymal stem cells

AU - Wang, Meijing

AU - Yu, Qing

AU - Wang, Lina

AU - Gu, Hongmei

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic capacity of MSCs and CSCs remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell fate commitment. Here we hypothesize that specific histone modifications accompany cardiac-specific gene expression, thus determining the differentiation capacity of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of gene activation, were higher in CSCs (Sca-1+CD29+) than MSCs. Additionally, lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led to increased cardiac gene expression and was accompanied by enhanced acH3 and acH4 levels at gene loci. We conclude that greater levels of histone acetylation at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for CSCs to develop into cardiomyocytes. These lineage-differential histone modifications are likely due to less HDAC recruitment at cardiac-specific gene promoters in CSCs than MSCs.

AB - Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic capacity of MSCs and CSCs remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell fate commitment. Here we hypothesize that specific histone modifications accompany cardiac-specific gene expression, thus determining the differentiation capacity of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of gene activation, were higher in CSCs (Sca-1+CD29+) than MSCs. Additionally, lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led to increased cardiac gene expression and was accompanied by enhanced acH3 and acH4 levels at gene loci. We conclude that greater levels of histone acetylation at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for CSCs to develop into cardiomyocytes. These lineage-differential histone modifications are likely due to less HDAC recruitment at cardiac-specific gene promoters in CSCs than MSCs.

KW - Cardiomyogenesis

KW - Epigenetic regulation

KW - Stem cell

UR - http://www.scopus.com/inward/record.url?scp=84878666988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878666988&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00359.2012

DO - 10.1152/ajpcell.00359.2012

M3 - Article

C2 - 23552285

AN - SCOPUS:84878666988

VL - 304

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 11

ER -