Emerin inhibits Lmo7 binding to the Pax3and MyoD promoters and expression of myoblast proliferation genes

Zinaida Dedeic, Maureen Cetera, Tatiana V. Cohen, James Holaska

Research output: Contribution to journalArticle

Abstract

X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP-Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.

Original languageEnglish (US)
Pages (from-to)1691-1702
Number of pages12
JournalDevelopment
Volume138
Issue number11
StatePublished - Jun 1 2011
Externally publishedYes

Fingerprint

Myoblasts
Genes
Emery-Dreifuss Muscular Dystrophy
T Cell Transcription Factor 1
emerin
Skeletal Muscle Fibers
Nuclear Envelope
Nuclear Proteins
Membrane Proteins
Cytoplasm
Down-Regulation
Gene Expression
Mutation

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Molecular Biology

Cite this

Dedeic, Zinaida ; Cetera, Maureen ; Cohen, Tatiana V. ; Holaska, James. / Emerin inhibits Lmo7 binding to the Pax3and MyoD promoters and expression of myoblast proliferation genes. In: Development. 2011 ; Vol. 138, No. 11. pp. 1691-1702.
@article{964293b552da4896821628f10fd5c156,
title = "Emerin inhibits Lmo7 binding to the Pax3and MyoD promoters and expression of myoblast proliferation genes",
abstract = "X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP-Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.",
author = "Zinaida Dedeic and Maureen Cetera and Cohen, {Tatiana V.} and James Holaska",
year = "2011",
month = "6",
day = "1",
language = "English (US)",
volume = "138",
pages = "1691--1702",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "11",

}

Emerin inhibits Lmo7 binding to the Pax3and MyoD promoters and expression of myoblast proliferation genes. / Dedeic, Zinaida; Cetera, Maureen; Cohen, Tatiana V.; Holaska, James.

In: Development, Vol. 138, No. 11, 01.06.2011, p. 1691-1702.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Emerin inhibits Lmo7 binding to the Pax3and MyoD promoters and expression of myoblast proliferation genes

AU - Dedeic, Zinaida

AU - Cetera, Maureen

AU - Cohen, Tatiana V.

AU - Holaska, James

PY - 2011/6/1

Y1 - 2011/6/1

N2 - X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP-Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.

AB - X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP-Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.

UR - http://www.scopus.com/inward/record.url?scp=79956360230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956360230&partnerID=8YFLogxK

M3 - Article

VL - 138

SP - 1691

EP - 1702

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 11

ER -