| Literature DB >> 29454939 |
Elisa Donnard1, Pranitha Vangala1, Shaked Afik2, Sean McCauley3, Anetta Nowosielska3, Alper Kucukural4, Barbara Tabak1, Xiaopeng Zhu1, William Diehl3, Patrick McDonel5, Nir Yosef6, Jeremy Luban7, Manuel Garber8.
Abstract
Most well-characterized enhancers are deeply conserved. In contrast, genome-wide comparative studies of steady-state systems showed that only a small fraction of active enhancers are conserved. To better understand conservation of enhancer activity, we used a comparative genomics approach that integrates temporal expression and epigenetic profiles in an innate immune system. We found that gene expression programs diverge among mildly induced genes, while being highly conserved for strongly induced genes. The fraction of conserved enhancers varies greatly across gene expression programs, with induced genes and early-response genes, in particular, being regulated by a higher fraction of conserved enhancers. Clustering of conserved accessible DNA sequences within enhancers resulted in over 60 sequence motifs including motifs for known factors, as well as many with unknown function. We further show that the number of instances of these motifs is a strong predictor of the responsiveness of a gene to pathogen detection.Entities:
Keywords: comparative genomics; enhancers; gene regulation; innate immunity; toll-like receptors
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Year: 2018 PMID： 29454939 PMCID： PMC5876141 DOI： 10.1016/j.cels.2018.01.002
Source DB: PubMed Journal: Cell Syst ISSN： 2405-4712 Impact factor: 10.304