Rapid and pervasive changes in genome-wide enhancer usage during mammalian development

Alexander 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

Research output: Contribution to journalArticle

182 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1521-1531
Number of pages11
JournalCell
Volume155
Issue number7
DOIs
StatePublished - Dec 19 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Nord, A., Blow, M. J., Attanasio, C., Akiyama, J. A., Holt, A., Hosseini, R., Phouanenavong, S., Plajzer-Frick, I., Shoukry, M., Afzal, V., Rubenstein, J. L. R., Rubin, E. M., Pennacchio, L. A., & Visel, A. (2013). Rapid and pervasive changes in genome-wide enhancer usage during mammalian development. Cell, 155(7), 1521-1531. https://doi.org/10.1016/j.cell.2013.11.033