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

Rapid and pervasive changes in genome-wide enhancer usage during mammalian development.
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DOI:
10.1016/j.cell.2013.11.033
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发表时间:
2013-12-19
期刊:
影响因子:
64.5
通讯作者:
Visel A
Visel A
中科院分区:
生物学1区
文献类型:
--
作者:
Nord AS;Blow MJ;Attanasio C;Akiyama JA;Holt A;Hosseini R;Phouanenavong S;Plajzer-Frick I;Shoukry M;Afzal V;Rubenstein JL;Rubin EM;Pennacchio LA;Visel A

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Enhancers are distal regulatory elements that can activate tissue-specific gene expression and are abundant throughout mammalian genomes. While substantial progress has been made towards 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 mid-gestation across all tissues examined. The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage underlying processes central to development and disease.
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