ChIP-seq Accurately Predicts Tissue-specific Activity of Enhancers

Overview

Journal Nature

Specialty Science

Date 2009 Feb 13

PMID 19212405

Citations 1018

Authors

Axel Visel

Matthew J Blow

Zirong Li

Tao Zhang

Jennifer A Akiyama

Amy Holt

Ingrid Plajzer-Frick

Malak Shoukry

Crystal Wright

Feng Chen

Veena Afzal

Bing Ren

Edward M Rubin

Len A Pennacchio

Affiliations

Soon will be listed here.

Abstract

A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

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