Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development

Esther E. Creemers, Lillian B. Sutherland, John McAnally, James A. Richardson, Eric N. Olson

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Myocardin is a transcriptional co-activator of serum response factor (Srf), which is a key regulator of the expression of smooth and cardiac muscle genes. Consistent with its role in regulating cardiovascular development, myocardin is the earliest known marker specific to both the cardiac and smooth muscle lineages during embryogenesis. To understand how the expression of this early transcriptional regulator is initiated and maintained, we scanned 90 kb of genomic DNA encompassing the myocardin gene for cisregulatory elements capable of directing myocardin transcription in cardiac and smooth muscle lineages in vivo. Here, we describe an enhancer that controls cardiovascular expression of the mouse myocardin gene during mouse embryogenesis and adulthood. Activity of this enhancer in the heart and vascular system requires the combined actions of the Mef2 and Foxo transcription factors. In addition, the Tead transcription factor is required specifically for enhancer activation in neural-crest-derived smooth muscle cells and dorsal aorta. Notably, myocardin also regulates its own enhancer, but in contrast to the majority of myocardin target genes, which are dependent on Srf, myocardin acts through Mef2 to control its enhancer. These findings reveal an Srf-independent mechanism for smooth and cardiac muscle-restricted transcription and provide insight into the regulatory mechanisms responsible for establishing the smooth and cardiac muscle phenotypes during development.

Original languageEnglish (US)
Pages (from-to)4245-4256
Number of pages12
JournalDevelopment
Volume133
Issue number21
DOIs
StatePublished - Nov 2006

Fingerprint

Smooth Muscle
Serum Response Factor
Myocardium
Proteins
Genes
Embryonic Development
Transcription Factors
myocardin
Neural Crest
Smooth Muscle Myocytes
Blood Vessels
Aorta
Phenotype
DNA

Keywords

  • Enhancer
  • Mouse
  • Myocardin
  • Smooth muscle
  • Transcriptional regulation
  • Transgene

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development. / Creemers, Esther E.; Sutherland, Lillian B.; McAnally, John; Richardson, James A.; Olson, Eric N.

In: Development, Vol. 133, No. 21, 11.2006, p. 4245-4256.

Research output: Contribution to journalArticle

Creemers, Esther E. ; Sutherland, Lillian B. ; McAnally, John ; Richardson, James A. ; Olson, Eric N. / Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development. In: Development. 2006 ; Vol. 133, No. 21. pp. 4245-4256.
@article{a646f891ccbd4ac9a848103a42f9acad,
title = "Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development",
abstract = "Myocardin is a transcriptional co-activator of serum response factor (Srf), which is a key regulator of the expression of smooth and cardiac muscle genes. Consistent with its role in regulating cardiovascular development, myocardin is the earliest known marker specific to both the cardiac and smooth muscle lineages during embryogenesis. To understand how the expression of this early transcriptional regulator is initiated and maintained, we scanned 90 kb of genomic DNA encompassing the myocardin gene for cisregulatory elements capable of directing myocardin transcription in cardiac and smooth muscle lineages in vivo. Here, we describe an enhancer that controls cardiovascular expression of the mouse myocardin gene during mouse embryogenesis and adulthood. Activity of this enhancer in the heart and vascular system requires the combined actions of the Mef2 and Foxo transcription factors. In addition, the Tead transcription factor is required specifically for enhancer activation in neural-crest-derived smooth muscle cells and dorsal aorta. Notably, myocardin also regulates its own enhancer, but in contrast to the majority of myocardin target genes, which are dependent on Srf, myocardin acts through Mef2 to control its enhancer. These findings reveal an Srf-independent mechanism for smooth and cardiac muscle-restricted transcription and provide insight into the regulatory mechanisms responsible for establishing the smooth and cardiac muscle phenotypes during development.",
keywords = "Enhancer, Mouse, Myocardin, Smooth muscle, Transcriptional regulation, Transgene",
author = "Creemers, {Esther E.} and Sutherland, {Lillian B.} and John McAnally and Richardson, {James A.} and Olson, {Eric N.}",
year = "2006",
month = "11",
doi = "10.1242/dev.02610",
language = "English (US)",
volume = "133",
pages = "4245--4256",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "21",

}

TY - JOUR

T1 - Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development

AU - Creemers, Esther E.

AU - Sutherland, Lillian B.

AU - McAnally, John

AU - Richardson, James A.

AU - Olson, Eric N.

PY - 2006/11

Y1 - 2006/11

N2 - Myocardin is a transcriptional co-activator of serum response factor (Srf), which is a key regulator of the expression of smooth and cardiac muscle genes. Consistent with its role in regulating cardiovascular development, myocardin is the earliest known marker specific to both the cardiac and smooth muscle lineages during embryogenesis. To understand how the expression of this early transcriptional regulator is initiated and maintained, we scanned 90 kb of genomic DNA encompassing the myocardin gene for cisregulatory elements capable of directing myocardin transcription in cardiac and smooth muscle lineages in vivo. Here, we describe an enhancer that controls cardiovascular expression of the mouse myocardin gene during mouse embryogenesis and adulthood. Activity of this enhancer in the heart and vascular system requires the combined actions of the Mef2 and Foxo transcription factors. In addition, the Tead transcription factor is required specifically for enhancer activation in neural-crest-derived smooth muscle cells and dorsal aorta. Notably, myocardin also regulates its own enhancer, but in contrast to the majority of myocardin target genes, which are dependent on Srf, myocardin acts through Mef2 to control its enhancer. These findings reveal an Srf-independent mechanism for smooth and cardiac muscle-restricted transcription and provide insight into the regulatory mechanisms responsible for establishing the smooth and cardiac muscle phenotypes during development.

AB - Myocardin is a transcriptional co-activator of serum response factor (Srf), which is a key regulator of the expression of smooth and cardiac muscle genes. Consistent with its role in regulating cardiovascular development, myocardin is the earliest known marker specific to both the cardiac and smooth muscle lineages during embryogenesis. To understand how the expression of this early transcriptional regulator is initiated and maintained, we scanned 90 kb of genomic DNA encompassing the myocardin gene for cisregulatory elements capable of directing myocardin transcription in cardiac and smooth muscle lineages in vivo. Here, we describe an enhancer that controls cardiovascular expression of the mouse myocardin gene during mouse embryogenesis and adulthood. Activity of this enhancer in the heart and vascular system requires the combined actions of the Mef2 and Foxo transcription factors. In addition, the Tead transcription factor is required specifically for enhancer activation in neural-crest-derived smooth muscle cells and dorsal aorta. Notably, myocardin also regulates its own enhancer, but in contrast to the majority of myocardin target genes, which are dependent on Srf, myocardin acts through Mef2 to control its enhancer. These findings reveal an Srf-independent mechanism for smooth and cardiac muscle-restricted transcription and provide insight into the regulatory mechanisms responsible for establishing the smooth and cardiac muscle phenotypes during development.

KW - Enhancer

KW - Mouse

KW - Myocardin

KW - Smooth muscle

KW - Transcriptional regulation

KW - Transgene

UR - http://www.scopus.com/inward/record.url?scp=33751534932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751534932&partnerID=8YFLogxK

U2 - 10.1242/dev.02610

DO - 10.1242/dev.02610

M3 - Article

C2 - 17021041

AN - SCOPUS:33751534932

VL - 133

SP - 4245

EP - 4256

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 21

ER -