TY - JOUR
T1 - Specialized compartments of cardiac nuclei exhibit distinct proteomic anatomy
AU - Franklin, Sarah
AU - Zhang, Michael J.
AU - Chen, Haodong
AU - Paulsson, Anna K.
AU - Mitchell-Jordan, Scherise A.
AU - Li, Yifeng
AU - Ping, Peipei
AU - Vondriska, Thomas M.
PY - 2011/1
Y1 - 2011/1
N2 - As host to the genome, the nucleus plays a critical role as modulator of cellular phenotype. To understand the totality of proteins that regulate this organelle, we used proteomics to characterize the components of the cardiac nucleus. Following purification, cardiac nuclei were fractionated into biologically relevant fractions including acid-soluble proteins, chromatin-bound molecules and nucleoplasmic proteins. These distinct subproteomes were characterized by liquid chromatography-tandem MS. We report a cardiac nuclear proteome of 1048 proteins-only 146 of which are shared between the distinct subcompartments of this organelle. Analysis of genomic loci encoding these molecules gives insights into local hotspots for nuclear protein regulation. High mass accuracy and complementary analytical techniques allowed the discrimination of distinct protein isoforms, including 54 total histone variants, 17 of which were distinguished by unique peptide sequences and four of which have never been detected at the protein level. These studies are the first unbiased analysis of cardiac nuclear subcompartments and provide a foundation for exploration of this organelle's proteomes during disease.
AB - As host to the genome, the nucleus plays a critical role as modulator of cellular phenotype. To understand the totality of proteins that regulate this organelle, we used proteomics to characterize the components of the cardiac nucleus. Following purification, cardiac nuclei were fractionated into biologically relevant fractions including acid-soluble proteins, chromatin-bound molecules and nucleoplasmic proteins. These distinct subproteomes were characterized by liquid chromatography-tandem MS. We report a cardiac nuclear proteome of 1048 proteins-only 146 of which are shared between the distinct subcompartments of this organelle. Analysis of genomic loci encoding these molecules gives insights into local hotspots for nuclear protein regulation. High mass accuracy and complementary analytical techniques allowed the discrimination of distinct protein isoforms, including 54 total histone variants, 17 of which were distinguished by unique peptide sequences and four of which have never been detected at the protein level. These studies are the first unbiased analysis of cardiac nuclear subcompartments and provide a foundation for exploration of this organelle's proteomes during disease.
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U2 - 10.1074/mcp.M110.000703
DO - 10.1074/mcp.M110.000703
M3 - Article
C2 - 20807835
AN - SCOPUS:78651096109
SN - 1535-9476
VL - 10
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 1
ER -