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PMID: 20729851 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

ChIP-Seq identification of weakly conserved heart enhancers.

Nature genetics ·Vol. 42 ·No. 9 ·2010-09-00 ·Pages 806-10

Blow MJ, McCulley DJ, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, Afzal V, Bristow J, Ren B, Black BL, Rubin EM, Visel A, Pennacchio LA

Abstract

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.

MeSH Terms
Animals Base Sequence Chromatin Immunoprecipitation/methods Conserved Sequence/genetics Embryo, Mammalian Enhancer Elements, Genetic/genetics Evolution, Molecular Gene Expression Regulation, Developmental Heart/embryology Humans Mice Mice, Transgenic Models, Biological Myocardium/metabolism Organ Specificity/genetics Phylogeny Sequence Analysis, DNA/methods Vertebrates/genetics,metabolism
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Blow Matthew J
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
McCulley David J
Li Zirong
Zhang Tao
Akiyama Jennifer A
Holt Amy
Plajzer-Frick Ingrid
Shoukry Malak
Wright Crystal
Chen Feng
Afzal Veena
Bristow James
Ren Bing
Black Brian L
Rubin Edward M
Visel Axel
Pennacchio Len A
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.650
Published
2010-09-00
Epub
2010-00-22
Pages
806-10
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3138496
Subset
IM
Grants
NHLBI NIH HHS · HL066681 · United States
NHLBI NIH HHS · R01 HL064658-11 · United States
NHGRI NIH HHS · HG003988 · United States
NIDCR NIH HHS · R01 DE019118 · United States
NHGRI NIH HHS · R01 HG003988-06 · United States
NHLBI NIH HHS · HL89707 · United States
NHLBI NIH HHS · P01 HL089707-04 · United States
NHLBI NIH HHS · R01 HL064658 · United States
NHLBI NIH HHS · HL64658 · United States
NHLBI NIH HHS · U01 HL066681 · United States
NHGRI NIH HHS · R01 HG003988 · United States
NHLBI NIH HHS · U01 HL066681-08 · United States
NHLBI NIH HHS · P01 HL089707 · United States
NIDCR NIH HHS · R01 DE019118-03 · United States
Databases
GEO
GSE13845, GSE22549
Corrections
CommentIn
PMID: 20802475
External Links
PubMed source DOI: 10.1038/ng.650 PMC Full Text View journal details
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