Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart

Zhiyv Niu, Dinakar Iyer, Simon Conway, James F. Martin, Kathryn Ivey, Deepak Srivastava, Alfred Nordheim, Robert J. Schwartz

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Our conditional serum response factor (SRF) knockout, SrfCko, in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the SrfCKO mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.

Original languageEnglish
Pages (from-to)17824-17829
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number46
DOIs
StatePublished - Nov 18 2008

Fingerprint

Serum Response Factor
Bone Morphogenetic Protein 4
Genes
Down-Regulation
Calcium-Activated Potassium Channels
Null Lymphocytes
Sarcomeres
Chromatin Assembly and Disassembly
Myofibrils
MicroRNAs
Muscle Cells
Proteins
Transcription Factors

Keywords

  • Cardiogenesis
  • GATA6
  • Heart development
  • MicroRNA
  • Periostin

ASJC Scopus subject areas

  • General

Cite this

Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart. / Niu, Zhiyv; Iyer, Dinakar; Conway, Simon; Martin, James F.; Ivey, Kathryn; Srivastava, Deepak; Nordheim, Alfred; Schwartz, Robert J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 46, 18.11.2008, p. 17824-17829.

Research output: Contribution to journalArticle

Niu, Zhiyv ; Iyer, Dinakar ; Conway, Simon ; Martin, James F. ; Ivey, Kathryn ; Srivastava, Deepak ; Nordheim, Alfred ; Schwartz, Robert J. / Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 46. pp. 17824-17829.
@article{f70919cf36e24d0d861f3cdd55a776ec,
title = "Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart",
abstract = "Our conditional serum response factor (SRF) knockout, SrfCko, in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the SrfCKO mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.",
keywords = "Cardiogenesis, GATA6, Heart development, MicroRNA, Periostin",
author = "Zhiyv Niu and Dinakar Iyer and Simon Conway and Martin, {James F.} and Kathryn Ivey and Deepak Srivastava and Alfred Nordheim and Schwartz, {Robert J.}",
year = "2008",
month = "11",
day = "18",
doi = "10.1073/pnas.0805491105",
language = "English",
volume = "105",
pages = "17824--17829",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "46",

}

TY - JOUR

T1 - Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart

AU - Niu, Zhiyv

AU - Iyer, Dinakar

AU - Conway, Simon

AU - Martin, James F.

AU - Ivey, Kathryn

AU - Srivastava, Deepak

AU - Nordheim, Alfred

AU - Schwartz, Robert J.

PY - 2008/11/18

Y1 - 2008/11/18

N2 - Our conditional serum response factor (SRF) knockout, SrfCko, in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the SrfCKO mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.

AB - Our conditional serum response factor (SRF) knockout, SrfCko, in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the SrfCKO mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.

KW - Cardiogenesis

KW - GATA6

KW - Heart development

KW - MicroRNA

KW - Periostin

UR - http://www.scopus.com/inward/record.url?scp=56649099185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56649099185&partnerID=8YFLogxK

U2 - 10.1073/pnas.0805491105

DO - 10.1073/pnas.0805491105

M3 - Article

VL - 105

SP - 17824

EP - 17829

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

ER -