ATAC-seq This composite track, "ATAC-seq", provides access and visualization to the signal for chromatin accessibility as measured using the Assay for Transposase Accessible Chromatin by Sequencing (Buenrostro et al. 2013) in many mouse blood cell types. The sequencing reads from the ATAC-seq experiments were mapped and analyzed using the VISION project pipelines (Xiang et al. 2024). The experiments were conducted in the VISION project and in the Amit lab for many primary blood cell types (Lara-Astiaso et al. 2014).
Peaks versus regions: Nuclease accessible regions tend to be long, e.g. 10 kb or longer. These accessible regions can contain entire genes or even clusters of genes. Within the nuclease accessible regions, some localized DNA segments are so readily cleaved that double-strand breaks are generated at that position in a substantial fraction of the cells in the population. These are the DNase-hypersensitive sites (DHSs) that are hallmarks of cis-regulatory elements. One can consider the "regions" as the equivalent of nuclease accessible regions, and the "peaks" as the equivalent of DHSs.
In "dense" mode, the display gives a compact view of the level of epigenetic signal for each feature in each cell type. In "full" mode, the normalized signal strength is shown as a continuous, variable signal. Users have options for setting the y-axis using the menus at the top of this Track Settings page. A y-axis setting of 0 to 0.5 is useful for visualizing these data.
Tracks to examine can be selected using the matrix of cell types and data sources provided at the top of this page or from the list of tracks. The matrix also gives a choice of data generated in the VISION project or by the Amit lab (Lara-Astiaso et al. 2014).
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.
ATAC-seq data from the immortalized cell lines G1E and G1E-ER4 are also provided. 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).
The ATAC-seq experiments used the methods described in Buenrostro et al. (2013), Corces et al. (2016), with data processing as described in Xiang et al. (2020 and 2024).
The data mapping and processing, downloads, generation of the tracks displayed, and development of the track hub were done by Belinda Giardine.
Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013 Dec;10(12):1213-8. doi: 10.1038/nmeth.2688. Epub 2013 Oct 6. PMID: 24097267; PMCID: PMC3959825.
Corces MR, Buenrostro JD, Wu B, Greenside PG, Chan SM, Koenig JL, Snyder MP, Pritchard JK, Kundaje A, Greenleaf WJ, Majeti R, Chang HY. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat Genet. 2016 Oct;48(10):1193-203. doi: 10.1038/ng.3646. Epub 2016 Aug 15. PMID: 27526324; PMCID: PMC5042844.
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.
Lara-Astiaso D, Weiner A, Lorenzo-Vivas E, Zaretsky I et al. Immunogenetics. Chromatin state dynamics during blood formation. Science 2014 Aug 22;345(6199):943-9. PMID: 25103404 GSE59992.
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