|Exploring Regulatory Function with Comparative Epigenomics|
|SciMed - Genetics & Genome|
|TS-Si News Service|
|Tuesday, 12 June 2012 12:00|
St. Louis, MO, USA. A method called comparative epigenomics uses interspecies comparison of DNA and histone modifications for in-depth annotation of the regulatory genome.
So far, sequencing of the human genome has provided a wealth of genetic information, but the goal of cataloguing the specific functions of every gene (and the collective interactions of all genes) has remained elusive.
While the genome of an organism contains all its genes, it is the epigenome that decides which are expressed (or turned on). Though genomic science has long focused on comparative genomics comparing the genomes of similar species and finding the commonalities to determine how common traits are regulated comparative epigenetics is intended as a more in-depth look at regulatory functions.
Click Pic for DetailsThe researchers were led by Sheng Zhong, of the Institute for Genomic Biology and Department of Bioengineering at the University of Illinois. Zhong collaborated with Ting Wang at Washington University in St. Louis, Harris Lewin, and Franklin West at the University of Georgia. They focused their work on three species: humans, mice, and pigs.
By analyzing 9 epigenomic marks in pluripotent stem cells, they were able to create an epigenomic map for each which they could then compare. The findings appear in the journal Cell.
The research team concluded that, with proper analysis procedures, traces of interspecies epigenomic conservation could be identified. They then demonstrated that the conserved epigenetic markers can be effectively used to annotate the genome, clarifying the genome's regulatory function.
Understanding the genome is one of the most pressing problems for science, and the investigators believe their study findings shed light on a promising alternative method. "Comparative epigenomics enables us to find more clues from evolution about the functions of our genomes," adds Zhong.
CitationComparative Epigenomic Annotation of Regulatory DNA. Shu Xiao, Dan Xie, Xiaoyi Cao, Pengfei Yu, Xiaoyun Xing, Chieh-Chun Chen, Meagan Musselman, Mingchao Xie, Franklin D. West, Harris A. Lewin, Ting Wang, Sheng Zhong. Cell 2012; 149(6): 1381-1392. doi:10.1016/j.cell.2012.04.029
● Epigenetic patterns of histone and DNA modification are conserved across species
● Epigenomic conservation occurs in both fast- and slow-evolving DNA sequences
● Changes in the epigenome, transcriptome, and protein-DNA binding patterns are correlated
● The conserved colocalization of different epigenetic marks defines regulatory DNA
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.
|Last Updated on Tuesday, 12 June 2012 12:07|