title: Rapid and pervasive changes in genome-wide enhancer usage during mammalian development.
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.
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Nord
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Blow
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Catia
authors.initials: C
authors.lastname: Attanasio
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Akiyama
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Holt
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Roya
authors.initials: R
authors.lastname: Hosseini
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Sengthavy
authors.initials: S
authors.lastname: Phouanenavong
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Plajzer-Frick
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Malak
authors.initials: M
authors.lastname: Shoukry
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Afzal
authors.affiliation: Department of Psychiatry, Rock Hall, University of California, San Francisco, CA 94158-2324, USA.
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA. Electronic address: lapennacchio@lbl.gov.
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA; School of Natural Sciences, University of California, Merced, CA 95343, USA. Electronic address: avisel@lbl.gov.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
mesh_terms: D000107:Acetylation; D000818:Animals; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity
chemical_list: D006657:Histones