LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions

Genome Biology

Duncan T. Odom¹  Diego Villar²  Aisling M. Redmond³  Louise Harewood⁴  Raghavendra Ramachanderan⁵  Osagie Izuogu⁵  Maša Roller⁵  Fergal Martin⁵  Ericca Stamper⁶  Paul Flicek⁷ 

[1] Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;German Cancer Research Center (DKFZ), Division of Regulatory Genomics and Cancer Evolution, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany;Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Present address: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK;Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Present address: MRC Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, CB2 0XZ, Cambridge, UK;Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Present address: Precision Medicine Centre of Excellence, Queen’s University Belfast, BT9 7AE, Belfast, UK;European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK;European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK;Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Present address: Harriet L. Wilkes Honors College, Florida Atlantic University, 33458, Jupiter, FL, USA;European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK;Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE, Cambridge, UK;Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK;

关键词: Regulatory evolution;    Gene regulation;    Promoters;    Enhancers;    Transposable elements;    Long Interspersed Nuclear Elements (LINEs);    LINE L1;    LINE L2;    Mammals;   

DOI  :  10.1186/s13059-021-02260-y

来源: Springer

【 摘 要 】

BackgroundTo 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.ResultsThe 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.ConclusionsOur analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.

【 授权许可】

CC BY