The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
| Autor: | Robert Sugar, Yulia Katsman, Elodie Darbo, Moorthy Sakthidevi, Lucas Brandon Edelman, Kristina Tabbada, Stefan Schoenfelder, Emilia Dimitrova, Biola M. Javierre, Filipe Tavares-Cadete, Borbala Mifsud, Simon Andrews, Andy Higgs, Bram Herman, Mayra Furlan-Magaril, Andrew Dimond, Peter Fraser, Steven W. Wingett, Jennifer A. Mitchell, Takashi Nagano, Cameron S. Osborne, Sarah Elderkin, Nicholas M. Luscombe, Emily M LeProust |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Resource
Bioinformatics Computational biology Biology Trans-regulatory element Epigenesis Genetic Histones Mice Genetics Animals Promoter Regions Genetic Transcription factor Genetics (clinical) ChIA-PET Locus control region Embryonic Stem Cells Regulation of gene expression Binding Sites Gene Expression Regulation Developmental Promoter 11 Medical And Health Sciences 06 Biological Sciences Chromatin Mice Inbred C57BL Enhancer Elements Genetic Liver Transcription Factor Gene Transcription Factors |
| Zdroj: | Schoenfelder, S, Furlan-Magaril, M, Mifsud, B, Tavares-Cadete, F, Sugar, R, Javierre, B M, Nagano, T, Katsman, Y, Sakthidevi, M, Wingett, S W, Dimitrova, E, Dimond, A, Edelman, L B, Elderkin, S, Tabbada, K, Darbo, E, Andrews, S, Herman, B, Higgs, A, LeProust, E, Osborne, C S, Mitchell, J A, Luscombe, N M & Fraser, P 2015, ' The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements ', Genome Research, vol. 25, no. 4, pp. 582-597 . https://doi.org/10.1101/gr.185272.114 |
| Popis: | The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression. |
| Databáze: | OpenAIRE |
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