ChIP-Seq identification of weakly conserved heart enhancers.
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.
Blow
Matthew J
MJ
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
McCulley
David J
DJ
Li
Zirong
Z
Zhang
Tao
T
Akiyama
Jennifer A
JA
Holt
Amy
A
Plajzer-Frick
Ingrid
I
Shoukry
Malak
M
Wright
Crystal
C
Chen
Feng
F
Afzal
Veena
V
Bristow
James
J
Ren
Bing
B
Black
Brian L
BL
Rubin
Edward M
EM
Visel
Axel
A
Pennacchio
Len A
LA
D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism