TY - JOUR
T1 - Comparative epigenomic annotation of regulatory DNA
AU - Xiao, Shu
AU - Xie, Dan
AU - Cao, Xiaoyi
AU - Yu, Pengfei
AU - Xing, Xiaoyun
AU - Chen, Chieh Chun
AU - Musselman, Meagan
AU - Xie, Mingchao
AU - West, Franklin D.
AU - Lewin, Harris A.
AU - Wang, Ting
AU - Zhong, Sheng
N1 - Funding Information:
This work was supported by NIH DP2-OD007417, NSF DBI 09-60583, and Sloan Research Fellowship to S.Z.; and by NIH 5U01ES017154, March of Dimes Foundation, Edward Jr. Mallinckrodt Foundation, DDRCC P30DK52574, and Siteman Cancer Center P50CA134254 to T.W. The authors thank Wei Huang and Darina McDee and Drs. Lisa Stubbs, Tetsuya Tanaka, Phillip Newmark, Rex Gaskins, Gene Robinson, David Clayton, Nigel Goldenfeld, Fei Wang, and Taekjip Ha for useful discussions.
PY - 2012/6/8
Y1 - 2012/6/8
N2 - Despite the explosive growth of genomic data, functional annotation of regulatory sequences remains difficult. Here, we introduce "comparative epigenomics" - interspecies comparison of DNA and histone modifications - as an approach for annotation of the regulatory genome. We measured in human, mouse, and pig pluripotent stem cells the genomic distributions of cytosine methylation, H2A.Z, H3K4me1/2/3, H3K9me3, H3K27me3, H3K27ac, H3K36me3, transcribed RNAs, and P300, TAF1, OCT4, and NANOG binding. We observed that epigenomic conservation was strong in both rapidly evolving and slowly evolving DNA sequences, but not in neutrally evolving sequences. In contrast, evolutionary changes of the epigenome and the transcriptome exhibited a linear correlation. We suggest that the conserved colocalization of different epigenomic marks can be used to discover regulatory sequences. Indeed, seven pairs of epigenomic marks identified exhibited regulatory functions during differentiation of embryonic stem cells into mesendoderm cells. Thus, comparative epigenomics reveals regulatory features of the genome that cannot be discerned from sequence comparisons alone.
AB - Despite the explosive growth of genomic data, functional annotation of regulatory sequences remains difficult. Here, we introduce "comparative epigenomics" - interspecies comparison of DNA and histone modifications - as an approach for annotation of the regulatory genome. We measured in human, mouse, and pig pluripotent stem cells the genomic distributions of cytosine methylation, H2A.Z, H3K4me1/2/3, H3K9me3, H3K27me3, H3K27ac, H3K36me3, transcribed RNAs, and P300, TAF1, OCT4, and NANOG binding. We observed that epigenomic conservation was strong in both rapidly evolving and slowly evolving DNA sequences, but not in neutrally evolving sequences. In contrast, evolutionary changes of the epigenome and the transcriptome exhibited a linear correlation. We suggest that the conserved colocalization of different epigenomic marks can be used to discover regulatory sequences. Indeed, seven pairs of epigenomic marks identified exhibited regulatory functions during differentiation of embryonic stem cells into mesendoderm cells. Thus, comparative epigenomics reveals regulatory features of the genome that cannot be discerned from sequence comparisons alone.
UR - http://www.scopus.com/inward/record.url?scp=84861977900&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.04.029
DO - 10.1016/j.cell.2012.04.029
M3 - Article
C2 - 22682255
AN - SCOPUS:84861977900
SN - 0092-8674
VL - 149
SP - 1381
EP - 1392
JO - Cell
JF - Cell
IS - 6
ER -