Rapid and Pervasive Changes in Genome-wide Enhancer Usage During Mammalian Development

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Dec 24

PMID 24360275

Citations 226

Authors

Alex S Nord

Matthew J Blow

Catia Attanasio

Jennifer A Akiyama

Amy Holt

Roya Hosseini

Sengthavy Phouanenavong

Ingrid Plajzer-Frick

Malak Shoukry

Veena Afzal

John L R Rubenstein

Edward M Rubin

Len A Pennacchio

Axel Visel

Affiliations

Soon will be listed here.

Abstract

Enhancers are distal regulatory elements that can activate tissue-specific gene expression and are abundant throughout mammalian genomes. Although substantial progress has been made toward genome-wide annotation of mammalian enhancers, their temporal activity patterns and global contributions in the context of developmental in vivo processes remain poorly explored. Here we used epigenomic profiling for H3K27ac, a mark of active enhancers, coupled to transgenic mouse assays to examine the genome-wide utilization of enhancers in three different mouse tissues across seven developmental stages. The majority of the ∼90,000 enhancers identified exhibited tightly temporally restricted predicted activity windows and were associated with stage-specific biological functions and regulatory pathways in individual tissues. Comparative genomic analysis revealed that evolutionary conservation of enhancers decreases following midgestation across all tissues examined. The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage that underlie processes central to development and disease.

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