Epigenome Map Reveals Regulatory Circuitry of Human Genome

Lara C. Pullen, PhD

March 04, 2015

A report from the National Institutes of Health Roadmap Epigenomics Program describes 111 reference epigenomes from cells taken from throughout the human body, as well as embryonic stem cells.

The Roadmap Epigenomics Consortium published the most comprehensive map of the human epigenome landscape online February 18 in Nature and deposited the data in an open access database. The main article describes the presence of epigenomic elements throughout the human body and also details the ability of these elements to regulate gene expression.

That article is accompanied by several additional papers that explore the role of the epigenome in embryonic development, as well as the development of disease, including cancer and Alzheimer's disease.

The epigenome maps will enable scientists to not only study genetic predisposition for disease but also examine environment-induced changes in the expression of the genes. The combination should open a window into the molecular underpinnings of nature and nurture, thereby helping scientists understand vulnerability to disease and the process of disease development.

For example, some of the findings from consortium researchers have reinforced assumed relationships between inflammatory bowel disease and the immune system.

Although the science is complex and the quantity of data enormous, Manolis Kellis, PhD, from the Massachusetts Institute of Technology in Cambridge, who is the corresponding author for the main article, was noticeably excited during a press conference as he described how scientists will be able to query the epigenomic database.

"We can now ask, using these maps of the 111 reference epigenomes, 'What are the cell types that contain regulatory regions that are active in each of the cell types and that overlap these genetic variants?' I think we're in for a surprise. That is what is really very exciting about these maps: They give us a completely unbiased picture," explained Dr Kellis.

From Genome to Epigenome

The Roadmap Epigenomics project builds on the Encyclopedia of DNA Elements (ENCODE) project launched by the US National Human Genome Research Institute in September 2003.

Although all cells in a person's body contain essentially the same genome, cellular identity is believed to be the result of their distinct epigenomes. Epigenomics is thus the study of the regulation of gene expression in the cell by key functional elements.

Epigenomic elements include methyl groups that tag DNA and histones, as well as transcription factors that bind to regulatory elements on DNA. Transcription factors differ between cell types and change during embryonic development; the changes are detailed in the current study.

The epigenome also contains information about the regulatory elements that lie within the DNA itself, such as elements in the promotor region and those in distant enhancer regions. The epigenome is thus the genetic regulatory circuitry, and its patterns reveal the accessibility of different genomic regions within different cell types.

Casey E. Romanoski, PhD, from the University of California, San Diego, in La Jolla, and colleagues, in an accompanying editorial, describe the importance of the project, as well as offer some caveats about the data.

Most important, they explain that much of the epigenomic data are taken from tissues and not pure cell populations. Thus, although the epigenome is likely unique for a given cell at a given point of time, the tissue samples integrate the epigenomic data over all of the cells in the given tissue sample.

The authors and editorialists have disclosed no relevant financial relationships.

Nature. Published online February 18, 2015. Article full text, Editorial full text

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