Document Detail


Detection of histone modifications at specific gene loci in single cells in histological sections.
MedLine Citation:
PMID:  23314172     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromatin immunoprecipitation assays have contributed greatly to our understanding of the role of histone modifications in gene regulation. However, they do not permit analysis with single-cell resolution, thus confounding analyses of heterogeneous cell populations. Here we present a method that permits visualization of histone modifications of single genomic loci with single-cell resolution in formaldehyde-fixed paraffin-embedded tissue sections based on combined use of in situ hybridization and proximity ligation assays. We show that dimethylation of lysine 4 of histone H3 (H3K4me2) at the MYH11 locus is restricted to the smooth muscle cell (SMC) lineage in human and mouse tissue sections and that the mark persists even in phenotypically modulated SMC in atherosclerotic lesions that show no detectable expression of SMC marker genes. This methodology has promise for broad applications in the study of epigenetic mechanisms in complex multicellular tissues in development and disease.
Authors:
Delphine Gomez; Laura S Shankman; Anh T Nguyen; Gary K Owens
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2013-01-13
Journal Detail:
Title:  Nature methods     Volume:  10     ISSN:  1548-7105     ISO Abbreviation:  Nat. Methods     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-30     Completed Date:  2013-03-28     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  101215604     Medline TA:  Nat Methods     Country:  United States    
Other Details:
Languages:  eng     Pagination:  171-7     Citation Subset:  IM    
Affiliation:
Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Data Bank Information
Bank Name/Acc. No.:
RefSeq/NG_009299;  NM_002474;  NM_013607
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MeSH Terms
Descriptor/Qualifier:
Animals
Atherosclerosis / metabolism
Cell Lineage
Chromatin Immunoprecipitation
Epigenesis, Genetic
Fixatives
Formaldehyde
Histones / metabolism*
Humans
In Situ Hybridization
Lysine / metabolism*
Male
Methylation
Mice
Myocytes, Smooth Muscle / metabolism
Myosin Heavy Chains / metabolism
Paraffin Embedding
Grant Support
ID/Acronym/Agency:
R01 HL038854/HL/NHLBI NIH HHS; R01 HL057353/HL/NHLBI NIH HHS; R01 HL087867/HL/NHLBI NIH HHS; R01 HL087867/HL/NHLBI NIH HHS; R01 HL098538/HL/NHLBI NIH HHS; R01 HL098538/HL/NHLBI NIH HHS; R01 HL57353/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fixatives; 0/Histones; 0/MYH11 protein, human; 0/Myosin Heavy Chains; 0/myosin 11, mouse; 50-00-0/Formaldehyde; 56-87-1/Lysine
Comments/Corrections
Comment In:
Nat Methods. 2013 Feb;10(2):117-8   [PMID:  23361091 ]

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