Genetic Variation in Enhancers Modifies Cardiomyopathy Gene Expression and Progression.
enhancer, polymorphisms
epigenomics
genes, modifier
lamin A/C
myosin heavy chain
tissue engineering
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
30 03 2021
30 03 2021
Historique:
pubmed:
23
1
2021
medline:
22
12
2021
entrez:
22
1
2021
Statut:
ppublish
Résumé
Inherited cardiomyopathy associates with a range of phenotypes, mediated by genetic and nongenetic factors. Noninherited cardiomyopathy also displays varying progression and outcomes. Expression of cardiomyopathy genes is under the regulatory control of promoters and enhancers, and human genetic variation in promoters and enhancers may contribute to this variability. We superimposed epigenomic profiling from hearts and cardiomyocytes, including promoter-capture chromatin conformation information, to identify enhancers for 2 cardiomyopathy genes, Multiple enhancers were identified and validated for Enhancers regulate cardiomyopathy gene expression, and genomic variation within these enhancer regions associates with cardiomyopathic progression over time. This integrated approach identified noncoding modifiers of cardiomyopathy and is applicable to other cardiac genes.
Sections du résumé
BACKGROUND
Inherited cardiomyopathy associates with a range of phenotypes, mediated by genetic and nongenetic factors. Noninherited cardiomyopathy also displays varying progression and outcomes. Expression of cardiomyopathy genes is under the regulatory control of promoters and enhancers, and human genetic variation in promoters and enhancers may contribute to this variability.
METHODS
We superimposed epigenomic profiling from hearts and cardiomyocytes, including promoter-capture chromatin conformation information, to identify enhancers for 2 cardiomyopathy genes,
RESULTS
Multiple enhancers were identified and validated for
CONCLUSIONS
Enhancers regulate cardiomyopathy gene expression, and genomic variation within these enhancer regions associates with cardiomyopathic progression over time. This integrated approach identified noncoding modifiers of cardiomyopathy and is applicable to other cardiac genes.
Identifiants
pubmed: 33478249
doi: 10.1161/CIRCULATIONAHA.120.050432
pmc: PMC8009836
mid: NIHMS1673296
doi:
Substances chimiques
MYH6 protein, human
0
MYH7 protein, human
0
Cardiac Myosins
EC 3.6.1.-
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1302-1316Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL128075
Pays : United States
Organisme : NHLBI NIH HHS
ID : F30 HL142187
Pays : United States
Organisme : NLM NIH HHS
ID : T32 LM012203
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL154712
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Commentaires et corrections
Type : CommentIn
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