Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes.

Publication ,  Journal Article
Monte, E; Mouillesseaux, K; Chen, H; Kimball, T; Ren, S; Wang, Y; Chen, J-N; Vondriska, TM; Franklin, S
Published in: Am J Physiol Heart Circ Physiol
December 1, 2013

Myocyte hypertrophy antecedent to heart failure involves changes in global gene expression, although the preceding mechanisms to coordinate DNA accessibility on a genomic scale are unknown. Chromatin-associated proteins alter chromatin structure by changing their association with DNA, thereby altering the gene expression profile. Little is known about the global changes in chromatin subproteomes that accompany heart failure, and the mechanisms by which these proteins alter chromatin structure. The present study tests the fundamental hypothesis that cardiac growth and plasticity in the setting of disease recapitulates conserved developmental chromatin remodeling events. We used quantitative proteomics to identify chromatin-associated proteins extracted via detergent and to quantify changes in their abundance during disease. Our study identified 321 proteins in this subproteome, demonstrating it to have modest conservation (37%) with that revealed using strong acid. Of these proteins, 176 exhibited altered expression during cardiac hypertrophy and failure; we conducted extensive functional characterization of one of these proteins, Nucleolin. Morpholino-based knockdown of nucleolin nearly abolished protein expression but surprisingly had little impact on gross morphological development. However, hearts of fish lacking Nucleolin displayed severe developmental impairment, abnormal chamber patterning and functional deficits, ostensibly due to defects in cardiac looping and myocyte differentiation. The mechanisms underlying these defects involve perturbed bone morphogenetic protein 4 expression, decreased rRNA transcription, and a shift to more heterochromatic chromatin. This study reports the quantitative analysis of a new chromatin subproteome in the normal and diseased mouse heart. Validation studies in the complementary model system of zebrafish examine the role of Nucleolin to orchestrate genomic reprogramming events shared between development and disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

December 1, 2013

Volume

305

Issue

11

Start / End Page

H1624 / H1638

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • Rats
  • RNA-Binding Proteins
  • RNA, Ribosomal
  • Proteomics
  • Phosphoproteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Monte, E., Mouillesseaux, K., Chen, H., Kimball, T., Ren, S., Wang, Y., … Franklin, S. (2013). Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes. Am J Physiol Heart Circ Physiol, 305(11), H1624–H1638. https://doi.org/10.1152/ajpheart.00529.2013
Monte, Emma, Kevin Mouillesseaux, Haodong Chen, Todd Kimball, Shuxun Ren, Yibin Wang, Jau-Nian Chen, Thomas M. Vondriska, and Sarah Franklin. “Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes.Am J Physiol Heart Circ Physiol 305, no. 11 (December 1, 2013): H1624–38. https://doi.org/10.1152/ajpheart.00529.2013.
Monte E, Mouillesseaux K, Chen H, Kimball T, Ren S, Wang Y, et al. Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2013 Dec 1;305(11):H1624–38.
Monte, Emma, et al. “Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes.Am J Physiol Heart Circ Physiol, vol. 305, no. 11, Dec. 2013, pp. H1624–38. Pubmed, doi:10.1152/ajpheart.00529.2013.
Monte E, Mouillesseaux K, Chen H, Kimball T, Ren S, Wang Y, Chen J-N, Vondriska TM, Franklin S. Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2013 Dec 1;305(11):H1624–H1638.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

December 1, 2013

Volume

305

Issue

11

Start / End Page

H1624 / H1638

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • Rats
  • RNA-Binding Proteins
  • RNA, Ribosomal
  • Proteomics
  • Phosphoproteins