Candidate cis-regulatory elements, or cCREs, colored by dominant epigenetic state This composite track displays the cCREs colored by the dominant epigenetic state found in that cCRE in each cell type (Xiang et al. 2024). Related resources in this track hub are the track cCREs, which is a compilation of all cCREs discovered in human blood cell types in the VISION project along with annotation of conservation and cross-cell type clustering, and the composite track IDEAS Epigenetic states, which has the epigenetic state assignments genome-wide across human blood cell types resulting from jointly analyzing the data in human and mouse. A guide to the epigenetic states is on the Track Settings page of the IDEAS Epigenetic states composite track.
In "dense" mode, the display shows the position of each cCRE, which is colored to indicate the epigenetic state that occupies the greatest portion of the cCRE in each cell type. The color codes for the epigenetic states are defined in the Description section of the composite track IDEAS Epigenetic states. In "pack" or "full" mode, the genomic intervals are further annotated with the shorthand for the function commonly associated with the combination of epigenetic features that make up the state. These include P for promoter and E for enhancer. The full listing is on the Track Settings page of the IDEAS Epigenetic states composite track.
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). These cells are capable of differentiation in vitro into more mature myeloid cells. 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 use of IDEAS in the IS mode for peak calling on chromatin accessibility data was described in Xiang et al. 2021 and Xiang et al. 2024. The multi-feature IDEAS segmentation on human and mouse epigenomes was described in Xiang et al. 2024.
The data normalization, the peak calls using IDEAS in the IS mode, and generation of the 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, Keller CA, Heuston E, Giardine BM, An L, Wixom AQ, Miller A, Cockburn A, Sauria MEG, Weaver K, Lichtenberg J, Göttgens B, Li Q, Bodine D, Mahony S, Taylor J, Blobel GA, Weiss MJ, Cheng Y, Yue F, Hughes J, Higgs DR, Zhang Y, Hardison RC. An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis. Genome Res. 2020 Mar;30(3):472-484. PMID: 32132109; PMCID: PMC7111515.
Xiang G, Keller CA, Giardine B, An L, Li Q, Zhang Y, Hardison RC. S3norm: simultaneous normalization of sequencing depth and signal-to-noise ratio in epigenomic data. Nucleic Acids Res. 2020 May 7;48(8):e43. doi:10.1093/nar/gkaa105. PMID: 32086521; PMCID: PMC7192629.
Xiang G, Giardine BM, Mahony S, Zhang Y, Hardison RC. S3V2-IDEAS: a package for normalizing, denoising and integrating epigenomic datasets across different cell types. Bioinformatics. 2021 Sep 29;37(18):3011-3013. doi:10.1093/bioinformatics/btab148. PMID: 33681991; PMCID: PMC8479670.
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