Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells.
Autor: | Moyers BA; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Partridge EC; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Mackiewicz M; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Betti MJ; Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA., Darji R; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Meadows SK; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Newberry KM; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Brandsmeier LA; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA., Wold BJ; Merkin Institute for Translational Research, California Institute of Technology, Pasadena, California 91125, USA., Mendenhall EM; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; rmyers@hudsonalpha.org emendenhall@hudsonalpha.org., Myers RM; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; rmyers@hudsonalpha.org emendenhall@hudsonalpha.org. |
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Jazyk: | angličtina |
Zdroj: | Genome research [Genome Res] 2023 Dec 01; Vol. 33 (11), pp. 1879-1892. Date of Electronic Publication: 2023 Dec 01. |
DOI: | 10.1101/gr.278205.123 |
Abstrakt: | Transcription factors (TFs) are trans -acting proteins that bind cis -regulatory elements (CREs) in DNA to control gene expression. Here, we analyzed the genomic localization profiles of 529 sequence-specific TFs and 151 cofactors and chromatin regulators in the human cancer cell line HepG2, for a total of 680 broadly termed DNA-associated proteins (DAPs). We used this deep collection to model each TF's impact on gene expression, and identified a cohort of 26 candidate transcriptional repressors. We examine high occupancy target (HOT) sites in the context of three-dimensional genome organization and show biased motif placement in distal-promoter connections involving HOT sites. We also found a substantial number of closed chromatin regions with multiple DAPs bound, and explored their properties, finding that a MAFF/MAFK TF pair correlates with transcriptional repression. Altogether, these analyses provide novel insights into the regulatory logic of the human cell line HepG2 genome and show the usefulness of large genomic analyses for elucidation of individual TF functions. (© 2023 Moyers et al.; Published by Cold Spring Harbor Laboratory Press.) |
Databáze: | MEDLINE |
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