The VISION Project The VISION project conducted a ValIdated Systematic IntegratiON of epigenetic datasets across progenitor and differentiated blood cell types in mouse and human (Heuston et al. 2018, Xiang et al. 2020, Xiang et al. 2024). The project was carried out by an international group of scientists funded by the National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health (grant R24DK106766) and with intramural support from the National Human Genome Research Institute. Key products and results of the project can be visualized on the UCSC Genome Browser using this track hub. The project website provides other servers, databases, and data downloads.
OnTAD for estimating hierarchical topologically associated domains (TADs) OnTAD is an optimized nested TAD caller that was developed to identify hierarchical TADs from Hi-C data (An et al. 2019). The spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed TADs, within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. Hence, OnTAD was developed to identify hierarchical structures of TADs and subTADs.
This composite track shows the result of OnTAD analysis of Hi-C data in two cell lines related to immature erythroblasts (G1E-ER4) and multipotential myeloid cells (HPC7). Boundaries and extent of TADs and subTADs can be visualized on these tracks.
Two types of tracks are provided: the boundaries of TADs and subTADs and the interval contained in a TAD or subTAD. The boundaries are annotated with the level of nesting for a TAD, with higher numbers (level 2, level 3, etc.) indicating a greater extent of nesting (An et al. 2019).
Multiple replicates of the Hi-C data were pooled, and the TADs were either called jointly across the replicates or not. The joint calls are likely more robust, and the jointly called tracks are recommended as the default.
The Hi-C data were from analysis of two 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). 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.
The methods for OnTAD are described in An et al. (2019).
Lin An computed the TADs and boundaries using OnTAD. Belinda Giardine generated the track and developed the track hub.
An L, Yang T, Yang J, Nuebler J, Xiang G, Hardison RC, Li Q, Zhang Y. OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries. Genome Biol. 2019 Dec 18;20(1):282. doi: 10.1186/s13059-019-1893-y. PMID: 31847870; PMCID: PMC6918570.
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Heuston EF, Keller CA, Lichtenberg J, Giardine B, Anderson SM; NIH Intramural Sequencing Center; Hardison RC, Bodine DM. Establishment of regulatory elements during erythro-megakaryopoiesis identifies hematopoietic lineage-commitment points. Epigenetics Chromatin. 2018 May 28;11(1):22. PMID: 29807547; PMCID: PMC5971425.
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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