Maša Roller1, Ericca Stamper1,2,3, Diego Villar2,4, Osagie Izuogu1, Fergal Martin1, Aisling M Redmond2,5, Raghavendra Ramachanderan1, Louise Harewood2,6, Duncan T Odom7,8, Paul Flicek9,10,11. 1. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. 2. Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK. 3. Present address: Harriet L. Wilkes Honors College, Florida Atlantic University, Jupiter, FL, 33458, USA. 4. Present address: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK. 5. Present address: MRC Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, CB2 0XZ, UK. 6. Present address: Precision Medicine Centre of Excellence, Queen's University Belfast, Belfast, BT9 7AE, UK. 7. Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK. d.odom@dkfz.de. 8. German Cancer Research Center (DKFZ), Division of Regulatory Genomics and Cancer Evolution, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. d.odom@dkfz.de. 9. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. flicek@ebi.ac.uk. 10. Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK. flicek@ebi.ac.uk. 11. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. flicek@ebi.ac.uk.
Abstract
BACKGROUND: To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals. RESULTS: The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species. CONCLUSIONS: Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.
BACKGROUND: To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals. RESULTS: The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species. CONCLUSIONS: Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.
Entities:
Keywords:
Enhancers; Gene regulation; LINE L1; LINE L2; Long Interspersed Nuclear Elements (LINEs); Mammals; Promoters; Regulatory evolution; Transposable elements
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