1. Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon
- Author
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William E. Diehl, Sean M. McCauley, Patrick McDonel, Jeremy Luban, Manuel Garber, Anetta Nowosielska, Alper Kucukural, Nir Yosef, Pranitha Vangala, Xiaopeng Zhu, Shaked Afik, Barbara Tabak, and Elisa Donnard
- Subjects
Male ,0301 basic medicine ,Histology ,Computational biology ,Biology ,Article ,Epigenesis, Genetic ,Pathology and Forensic Medicine ,Evolution, Molecular ,Mice ,03 medical and health sciences ,Gene expression ,Animals ,Humans ,Epigenetics ,Enhancer ,Gene ,Conserved Sequence ,Regulation of gene expression ,Comparative genomics ,Innate immune system ,Toll-Like Receptors ,Genomics ,Cell Biology ,Immunity, Innate ,Mice, Inbred C57BL ,Enhancer Elements, Genetic ,030104 developmental biology ,Gene Expression Regulation ,Female ,Sequence motif - Abstract
Summary 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.
- Published
- 2018
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