Expression and functional activity of four myocardin isoforms

Masaaki Imamura, Xiaochun Long, Vivek Nanda, Joseph M. Miano

Research output: Contribution to journalArticle

Abstract

Myocardin (MYOCD) is an essential component of a molecular switch for the expression of contractile genes in smooth muscle and cardiac muscle cells. The Myocd gene comprises at least fifteen exons, including two alternately spliced exons designated 2a and 10a. We investigated tissue-specific Myocd expression in mouse, rat and human tissues to determine the conservation in expression of each Myocd splice variant and to ascertain whether any functional differences exist among MYOCD isoforms. Conventional and quantitative RT-PCR revealed the dominant expression of Myocd exon 2a (Myocd_v3) in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart across all species studied. Each species of heart showed primarily a longer version of Myocd (Myocd_v1) without exon 2a. While exclusion of exon 2a was common in all cardiac muscle samples, exon skipping of Myocd exon 10a was a rare event in both cardiac muscle and SMC tissues. In general, all four MYOCD isoforms showed comparable stimulation of SMC promoters. On the other hand, Myocd_v1 and Myocd_v2 were more active than Myocd_v3 and Myocd_v4 in stimulating cardiac muscle promoters and Myocd_v1's activity was augmented in the presence of the cardiac transcription factor, MEF2C. Importantly, whereas all four MYOCD isoforms similarly induced expression of endogenous SMC genes in a prostate tumor cell line (LNCaP), none could induce the endogenous expression of specific cardiac markers. These results are the first to show relative expression and activities of the major myocardin isoforms across disparate species. We propose a new myocardin nomenclature reflecting the dominant splice variants expressed in cardiac muscle (Myocd_v1 and v2) versus SMC-rich tissues (Myocd_v3 and v4).

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalGene
Volume464
Issue number1-2
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Exons
Protein Isoforms
Smooth Muscle Myocytes
Myocardium
MEF2 Transcription Factors
myocardin
Tumor Cell Line
Cardiac Myocytes
Terminology
Genes
Smooth Muscle
Aorta
Prostate
Urinary Bladder
Gene Expression
Muscles
Polymerase Chain Reaction

Keywords

  • Comparative genomics
  • Gene expression
  • Myocardin
  • Promoter
  • Smooth muscle
  • Splicing

ASJC Scopus subject areas

  • Genetics

Cite this

Imamura, M., Long, X., Nanda, V., & Miano, J. M. (2010). Expression and functional activity of four myocardin isoforms. Gene, 464(1-2), 1-10. https://doi.org/10.1016/j.gene.2010.03.012

Expression and functional activity of four myocardin isoforms. / Imamura, Masaaki; Long, Xiaochun; Nanda, Vivek; Miano, Joseph M.

In: Gene, Vol. 464, No. 1-2, 01.09.2010, p. 1-10.

Research output: Contribution to journalArticle

Imamura, M, Long, X, Nanda, V & Miano, JM 2010, 'Expression and functional activity of four myocardin isoforms', Gene, vol. 464, no. 1-2, pp. 1-10. https://doi.org/10.1016/j.gene.2010.03.012
Imamura, Masaaki ; Long, Xiaochun ; Nanda, Vivek ; Miano, Joseph M. / Expression and functional activity of four myocardin isoforms. In: Gene. 2010 ; Vol. 464, No. 1-2. pp. 1-10.
@article{4e86e1a5143f409fa6d685fbb589d488,
title = "Expression and functional activity of four myocardin isoforms",
abstract = "Myocardin (MYOCD) is an essential component of a molecular switch for the expression of contractile genes in smooth muscle and cardiac muscle cells. The Myocd gene comprises at least fifteen exons, including two alternately spliced exons designated 2a and 10a. We investigated tissue-specific Myocd expression in mouse, rat and human tissues to determine the conservation in expression of each Myocd splice variant and to ascertain whether any functional differences exist among MYOCD isoforms. Conventional and quantitative RT-PCR revealed the dominant expression of Myocd exon 2a (Myocd_v3) in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart across all species studied. Each species of heart showed primarily a longer version of Myocd (Myocd_v1) without exon 2a. While exclusion of exon 2a was common in all cardiac muscle samples, exon skipping of Myocd exon 10a was a rare event in both cardiac muscle and SMC tissues. In general, all four MYOCD isoforms showed comparable stimulation of SMC promoters. On the other hand, Myocd_v1 and Myocd_v2 were more active than Myocd_v3 and Myocd_v4 in stimulating cardiac muscle promoters and Myocd_v1's activity was augmented in the presence of the cardiac transcription factor, MEF2C. Importantly, whereas all four MYOCD isoforms similarly induced expression of endogenous SMC genes in a prostate tumor cell line (LNCaP), none could induce the endogenous expression of specific cardiac markers. These results are the first to show relative expression and activities of the major myocardin isoforms across disparate species. We propose a new myocardin nomenclature reflecting the dominant splice variants expressed in cardiac muscle (Myocd_v1 and v2) versus SMC-rich tissues (Myocd_v3 and v4).",
keywords = "Comparative genomics, Gene expression, Myocardin, Promoter, Smooth muscle, Splicing",
author = "Masaaki Imamura and Xiaochun Long and Vivek Nanda and Miano, {Joseph M.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1016/j.gene.2010.03.012",
language = "English (US)",
volume = "464",
pages = "1--10",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Expression and functional activity of four myocardin isoforms

AU - Imamura, Masaaki

AU - Long, Xiaochun

AU - Nanda, Vivek

AU - Miano, Joseph M.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Myocardin (MYOCD) is an essential component of a molecular switch for the expression of contractile genes in smooth muscle and cardiac muscle cells. The Myocd gene comprises at least fifteen exons, including two alternately spliced exons designated 2a and 10a. We investigated tissue-specific Myocd expression in mouse, rat and human tissues to determine the conservation in expression of each Myocd splice variant and to ascertain whether any functional differences exist among MYOCD isoforms. Conventional and quantitative RT-PCR revealed the dominant expression of Myocd exon 2a (Myocd_v3) in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart across all species studied. Each species of heart showed primarily a longer version of Myocd (Myocd_v1) without exon 2a. While exclusion of exon 2a was common in all cardiac muscle samples, exon skipping of Myocd exon 10a was a rare event in both cardiac muscle and SMC tissues. In general, all four MYOCD isoforms showed comparable stimulation of SMC promoters. On the other hand, Myocd_v1 and Myocd_v2 were more active than Myocd_v3 and Myocd_v4 in stimulating cardiac muscle promoters and Myocd_v1's activity was augmented in the presence of the cardiac transcription factor, MEF2C. Importantly, whereas all four MYOCD isoforms similarly induced expression of endogenous SMC genes in a prostate tumor cell line (LNCaP), none could induce the endogenous expression of specific cardiac markers. These results are the first to show relative expression and activities of the major myocardin isoforms across disparate species. We propose a new myocardin nomenclature reflecting the dominant splice variants expressed in cardiac muscle (Myocd_v1 and v2) versus SMC-rich tissues (Myocd_v3 and v4).

AB - Myocardin (MYOCD) is an essential component of a molecular switch for the expression of contractile genes in smooth muscle and cardiac muscle cells. The Myocd gene comprises at least fifteen exons, including two alternately spliced exons designated 2a and 10a. We investigated tissue-specific Myocd expression in mouse, rat and human tissues to determine the conservation in expression of each Myocd splice variant and to ascertain whether any functional differences exist among MYOCD isoforms. Conventional and quantitative RT-PCR revealed the dominant expression of Myocd exon 2a (Myocd_v3) in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart across all species studied. Each species of heart showed primarily a longer version of Myocd (Myocd_v1) without exon 2a. While exclusion of exon 2a was common in all cardiac muscle samples, exon skipping of Myocd exon 10a was a rare event in both cardiac muscle and SMC tissues. In general, all four MYOCD isoforms showed comparable stimulation of SMC promoters. On the other hand, Myocd_v1 and Myocd_v2 were more active than Myocd_v3 and Myocd_v4 in stimulating cardiac muscle promoters and Myocd_v1's activity was augmented in the presence of the cardiac transcription factor, MEF2C. Importantly, whereas all four MYOCD isoforms similarly induced expression of endogenous SMC genes in a prostate tumor cell line (LNCaP), none could induce the endogenous expression of specific cardiac markers. These results are the first to show relative expression and activities of the major myocardin isoforms across disparate species. We propose a new myocardin nomenclature reflecting the dominant splice variants expressed in cardiac muscle (Myocd_v1 and v2) versus SMC-rich tissues (Myocd_v3 and v4).

KW - Comparative genomics

KW - Gene expression

KW - Myocardin

KW - Promoter

KW - Smooth muscle

KW - Splicing

UR - http://www.scopus.com/inward/record.url?scp=77955269556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955269556&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2010.03.012

DO - 10.1016/j.gene.2010.03.012

M3 - Article

C2 - 20385216

AN - SCOPUS:77955269556

VL - 464

SP - 1

EP - 10

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1-2

ER -