Beta coefficient scores The beta coefficients are estimates of the contribution of an epigenetic state to the level of expression of target genes; they were determined from a multivariate regression of epigenetic states in cCREs across cell types against the level of target gene expression across cell types (Xiang et al. 2020 and 2024). The epigenetic states were determined using the IDEAS genome segmentation and annotation system; they are displayed on the companion track IDEAS human-mouse, which is in the super track Epigenetic states. Each of the 25 epigenetic states has a beta coefficient score, and the states and scores were assigned in 200 bp windows for the epigenomes of each cell type. These scores are genome-wide except in blacklisted regions.
In "dense" mode, the display shows a gray-scale visualization of the beta coefficient for each 200bp window in each cell type. In "full" mode, the values of the beta coefficients are plotted as a continuous variable along the chromosomes for each cell type. Useful settings for the data range (y-axis) are from -0.1 to 0.5.
The track names (short name and the end of the long name) 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 multivariate regression and beta coefficients are described in Xiang et al. (2024) and on the Track Settings page for the parent super track Epigenetic state Regulatory Potential.
The multivariate regression and determination of beta coefficients were done by Guanjue Xiang. Belinda Giardine calculated the beta coefficients genome-wide, generated the tracks displayed, and developed the track hub.
Gregory T, Yu C, Ma A, Orkin SH, Blobel GA, Weiss MJ. GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression. Blood. 1999; 94:87-96. PMID: 10381501.
Pinto do O P, Richter K, Carlsson L. Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo. Blood. 2002 Jun 1;99(11):3939-46. doi: 10.1182/blood.v99.11.3939. PMID: 12010792.
Weiss MJ, Yu C, Orkin SH. Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line. Mol Cell Biol. 1997; 17:1642-1651. PMID: 9032291; PMCID: PMC231889.
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, 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