Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes
Year: 2024
Type: preprint
Abstract: -regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment.
Source: Genome Research
Authors: Guanjue Xiang, Xi He, Belinda M. Giardine, Kathryn J. Isaac, Dylan J. Taylor, Rajiv C. McCoy, Camden Jansen, Cheryl A. Keller, Alexander Q. Wixom, April Cockburn, Amber Miller, Qian Qi, Yanghua He, Yichao Li, Jens Lichtenberg, Elisabeth F. Heuston, Stacie M. Anderson, Jing Luan, Marit W. Vermunt, Feng Yue, Michael E.G. Sauria, Michael C. Schatz, James Taylor, Berthold Göttgens, Jim R. Hughes, Douglas R. Higgs, Mitchell J. Weiss, Yong Cheng, Gerd A. Blobel, David M. Bodine, Yu Zhang, Qunhua Li, Shaun Mahony, Ross C. Hardison
Institutions: Pennsylvania State University, Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Johns Hopkins University, St. Jude Children's Research Hospital, University of Hawaiʻi at Mānoa, National Institutes of Health, National Human Genome Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania, Northwestern University, Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, University of Oxford, MRC Weatherall Institute of Molecular Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, National Institutes of Health, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Statistical methods for improving reproducibility and utility of chromatin interaction data, G2661591086, G3147485722, G3489442295, G3555303909, G469708262, G539390710, G5527492078, A 2D segmentation method for jointly characterizing epigenetic dynamics in multiple cell lines, G6831373058, CAREER: Predicting transcription factor binding dynamics across cell types and species, G7292902093, G8084983523, 22-BBSRC/NSF-BIO Building synthetic regulatory units to understand the complexity of mammalian gene expression, G9000088201, G9000139069, G9000259701, G9000309741, G9000334939, G97735468
OpenAlex ID: W4400180108