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Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes
- Source :
- American journal of physiology. Heart and circulatory physiology, vol 305, iss 11, Monte, E; Mouillesseaux, K; Chen, H; Kimball, T; Ren, S; Wang, Y; et al.(2013). Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes. American Journal of Physiology-Heart and Circulatory Physiology, 305(11), H1624-H1638. doi: 10.1152/ajpheart.00529.2013. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1sn1w7m3
- Publication Year :
- 2013
- Publisher :
- eScholarship, University of California, 2013.
-
Abstract
- 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. © 2013 the American Physiological Society.
- Subjects :
- Proteomics
Male
Time Factors
Transcription, Genetic
Physiology
Medical Physiology
Bone Morphogenetic Protein 4
Cardiovascular
Mice
Gene expression
2.1 Biological and endogenous factors
Myocytes, Cardiac
Gene Knock-In Techniques
Zebrafish
Cells, Cultured
Inbred BALB C
Genetics
Mice, Inbred BALB C
Cultured
biology
cardiac hypertrophy
RNA-Binding Proteins
Chromatin
Cell biology
Heart Disease
Gene Knockdown Techniques
Cardiology and Cardiovascular Medicine
Cardiac
Transcription
Muscle Mechanics and Ventricular Function
Signal Transduction
Biotechnology
Cells
1.1 Normal biological development and functioning
Quantitative proteomics
Cardiomegaly
BMP4
Chromatin remodeling
nucleolin
Genetic
Physiology (medical)
Animals
Ribosomal
Heart Failure
Myocytes
Animal
Human Genome
Zebrafish Proteins
biology.organism_classification
Phosphoproteins
Chromatin Assembly and Disassembly
RRNA transcription
Rats
Disease Models, Animal
Gene Expression Regulation
Cardiovascular System & Hematology
RNA, Ribosomal
Disease Models
RNA
Nucleolin
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology, vol 305, iss 11, Monte, E; Mouillesseaux, K; Chen, H; Kimball, T; Ren, S; Wang, Y; et al.(2013). Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes. American Journal of Physiology-Heart and Circulatory Physiology, 305(11), H1624-H1638. doi: 10.1152/ajpheart.00529.2013. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1sn1w7m3
- Accession number :
- edsair.doi.dedup.....27b0c1a9f5532311670c7dfdd973b63b