Epigenetic states from IDEAS human-mouse joint segmentation This composite track displays the epigenetic states determined by jointly modeling human and mouse blood cell epigenomes using the IDEAS genome segmentation and annotation system (Xiang et al. 2024). The states were learned in an iterative process that included input of states learned in one species into the modeling of states in the other species, leading to a 25 state model with the same states in each species.
The normalized epigenetic signals used as input were chromatin accessibility from ATAC-seq, CTCF occupancy, and levels of the histone modifications H3K27ac, H3K27me3, H3K36me3, H3K4me1, H3K4me3, and H3K9me3 in multiple blood cell types. The tracks show state annotations across the genome in each of the mouse blood cell types.
In "dense" mode, the display gives a compact view of the epigenetic landscape in each cell type. In "pack" or "full" mode, the genomic intervals are annotated with the number of the chromatin state in each cell type, which can distinguish between states with similar colors.
The track names give an abbreviation for the blood cell type and replicate number (r1 or r2). Mouse primary blood cells purified predominantly using cell surface markers include: LSK = Lin-Sca1+Kit+ cells from mouse bone marrow containing hematopoietic stem and progenitor cells, CMP = common myeloid progenitor cell, MEP = megakaryocyte-erythrocyte progenitor cell, ERY = erythroblast, GMP = granulocyte monocyte progenitor cell, MON = monocyte, NEU = neutrophil, CLP = common lymphoid progenitor cell, B = B cell, NK = natural killer cell, T_CD4 = CD4+ T cell, T_CD8 = CD8+ T cell, CFUE = colony forming unit erythroid, fl = designates ERY derived from fetal liver, ad = designates ERY derived from adult bone marrow, CFUMK = colony forming unit megakaryocyte, iMK = immature megakaryocyte, MK_fl = megakaryocyte derived from fetal liver. AVE is a track with state assignments based on the average signal for each epigenetic feature across cell types.
Data from several immortalized cell lines were included. The G1E cells are an immortalized, GATA1-null cell line derived from mouse embryonic stem cells by gene targeting; these cells proliferate in culture as immature erythroid progenitor cells (Weiss, Yu, Orkin 1997). A stable subline of these cells, called G1E-ER4, undergoes terminal erythroid maturation when GATA1 function is restored as an activatable fusion of GATA1 to the ligand-binding domain of the estrogen receptor (ER). Untreated G1E-ER4 cells, carrying the inactive GATA1-ER, proliferate without differentiation, but treatment with estradiol (E2) activates the hybrid protein, effectively complementing the GATA1 loss-of-function and allowing synchronous erythroid differentiation and maturation (Gregory et al. 1999). An additional cell line model used here are murine erythroleukemia (MEL) cells, which can be chemically induced to mature into erythroblast-like cells with increased hemoglobin (iMEL). HPC7 cells are an immortalized line that serves as a model for mouse hematopoietic progenitor cells (Pinto do O 2002). CH12 cells are an immortalized line that is a model for mouse B cells; the epigenetic data on CH12 cells were used to generate the B cell epigenetic state annotation.
The genome-wide signals for the epigenetic features were normalized across cell types using the S3V2 version of S3norm in the pipeline S3V2-IDEAS (Xiang et al. 2020 and 2021). The joint modeling of epigenetic states in human and mouse is described in Xiang et al. (2024).
The data normalization and multi-feature IDEAS segmentation on human and mouse epigenomes were done by Guanjue Xiang. The data downloads, re-mapping and processing, generation of the tracks displayed, and development of the track hub were done by Belinda Giardine.
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Xiang G, He X, Giardine BM, Isaac KJ, Taylor DJ, McCoy RC, Jansen C, Keller CA, Wixom AQ, Cockburn A, Miller A, Qi Q, He Y, Li Y, Lichtenberg J, Heuston EF, Anderson SM, Luan J, Vermunt MW, Yue F, Sauria MEG, Schatz MC, Taylor J, Göttgens B, Hughes JR, Higgs DR, Weiss MJ, Cheng Y, Blobel GA, Bodine DM, Zhang Y, Li Q, Mahony S, Hardison RC. Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes. Genome Res. 2024 Aug 20;34(7):1089-1105. PMID: 38951027; PMCID: PMC11368181.
These data are available for use without restrictions.
Ross Hardison rch8@psu.edu