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Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth.

Publication ,  Journal Article
Franklin, S; Chen, H; Mitchell-Jordan, S; Ren, S; Wang, Y; Vondriska, TM
Published in: Mol Cell Proteomics
June 2012

A fundamental question in biology is how genome-wide changes in gene expression are enacted in response to a finite stimulus. Recent studies have mapped changes in nucleosome localization, determined the binding preferences for individual transcription factors, and shown that the genome adopts a nonrandom structure in vivo. What remains unclear is how global changes in the proteins bound to DNA alter chromatin structure and gene expression. We have addressed this question in the mouse heart, a system in which global gene expression and massive phenotypic changes occur without cardiac cell division, making the mechanisms of chromatin remodeling centrally important. To determine factors controlling genomic plasticity, we used mass spectrometry to measure chromatin-associated proteins. We have characterized the abundance of 305 chromatin-associated proteins in normal cells and measured changes in 108 proteins that accompany the progression of heart disease. These studies were conducted on a high mass accuracy instrument and confirmed in multiple biological replicates, facilitating statistical analysis and allowing us to interrogate the data bioinformatically for modules of proteins involved in similar processes. Our studies reveal general principles for global shifts in chromatin accessibility: altered linker to core histone ratio; differing abundance of chromatin structural proteins; and reprogrammed histone post-translational modifications. Using small interfering RNA-mediated loss-of-function in isolated cells, we demonstrate that the non-histone chromatin structural protein HMGB2 (but not HMGB1) suppresses pathologic cell growth in vivo and controls a gene expression program responsible for hypertrophic cell growth. Our findings reveal the basis for alterations in chromatin structure necessary for genome-wide changes in gene expression. These studies have fundamental implications for understanding how global chromatin remodeling occurs with specificity and accuracy, demonstrating that isoform-specific alterations in chromatin structural proteins can impart these features.

Duke Scholars

Published In

Mol Cell Proteomics

DOI

EISSN

1535-9484

Publication Date

June 2012

Volume

11

Issue

6

Start / End Page

M111.014258

Location

United States

Related Subject Headings

  • RNA Interference
  • Proteome
  • Myocardium
  • Mice, Inbred BALB C
  • Mice
  • Male
  • HMGB2 Protein
  • HMGB1 Protein
  • Gene Knockdown Techniques
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
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Franklin, S., Chen, H., Mitchell-Jordan, S., Ren, S., Wang, Y., & Vondriska, T. M. (2012). Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth. Mol Cell Proteomics, 11(6), M111.014258. https://doi.org/10.1074/mcp.M111.014258
Franklin, Sarah, Haodong Chen, Scherise Mitchell-Jordan, Shuxun Ren, Yibin Wang, and Thomas M. Vondriska. “Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth.Mol Cell Proteomics 11, no. 6 (June 2012): M111.014258. https://doi.org/10.1074/mcp.M111.014258.
Franklin S, Chen H, Mitchell-Jordan S, Ren S, Wang Y, Vondriska TM. Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth. Mol Cell Proteomics. 2012 Jun;11(6):M111.014258.
Franklin, Sarah, et al. “Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth.Mol Cell Proteomics, vol. 11, no. 6, June 2012, p. M111.014258. Pubmed, doi:10.1074/mcp.M111.014258.
Franklin S, Chen H, Mitchell-Jordan S, Ren S, Wang Y, Vondriska TM. Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth. Mol Cell Proteomics. 2012 Jun;11(6):M111.014258.

Published In

Mol Cell Proteomics

DOI

EISSN

1535-9484

Publication Date

June 2012

Volume

11

Issue

6

Start / End Page

M111.014258

Location

United States

Related Subject Headings

  • RNA Interference
  • Proteome
  • Myocardium
  • Mice, Inbred BALB C
  • Mice
  • Male
  • HMGB2 Protein
  • HMGB1 Protein
  • Gene Knockdown Techniques
  • Gene Expression Regulation