domingo, 22 de febrero de 2015

Epigenomics: Roadmap for regulation : Nature : Nature Publishing Group

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Epigenomics: Roadmap for regulation : Nature : Nature Publishing Group

Epigenomics: Roadmap for regulation

Published online
A package of papers investigates the functional regulatory elements in genomes that have been obtained from human tissue samples and cell lines. The implications of the project are presented here from three viewpoints. See Articles p.317p.331p.337 & p.344 and Letters p.350p.355p.360 & p.365

The topic in brief

  • Epigenomics is the study of the key functional elements that regulate gene expression in a cell.
  • Epigenomes provide information about the patterns in which structures such as methyl groups tag DNA and histones (the proteins around which DNA is packaged to form chromatin), and about interactions between distant sections of chromatin.
  • They also contain information about regulatory elements in DNA itself: both those that lie in the promoter region immediately upstream of where a gene's transcription begins, and those in distant enhancer sequences.
  • The ENCODE Project1 aimed to catalogue the regulatory elements in human cells, studying the epigenomic signatures of cells grown in culture. The Roadmap Epigenomics Project23,456789 builds on this by analysing samples taken directly from human tissues and cells — embryonic and adult, diseased and healthy (Fig. 1).
  • The researchers have linked these epigenomic data to the corresponding genetic information, producing reference epigenomes for 127 tissue and cell types.
  • The result is a representation of how epigenomic elements regulate gene expression in the human body.
Figure 1: From body to bench.
From body to bench.
The Roadmap Epigenomics Project has produced reference epigenomes that provide information on key functional elements controlling gene expression in 127 human tissues and cell types23456789, and encompassing embryonic and adult tissues, from healthy individuals and those with disease. a, Many of the adult tissues investigated were broken down by cell type or region — blood into several types of immune cell, for instance, and the brain into regions including the hippocampus and dorsolateral prefrontal cortex. Tissue samples and cells were subjected to a range of epigenomic analyses, along with genome sequencing and genome-wide association studies (GWAS). b, Embryonic stem (ES) cells, which are taken from the embryo at the 'blastocyst' stage and can give rise to almost every cell type in the body, were used to analyse, for example, the differentiation of stem cells into different neuronal lineages. The ES-cell-derived cell lines underwent the same epigenomic analyses as the tissue samples.

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