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vol1/fastq/ERR100/087/ERR10047687/ERR10047687_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/ERR100/085/ERR10047685/ERR10047685_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/ERR100/084/ERR10047684/ERR10047684_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/ERR100/082/ERR10047682/ERR10047682_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/ERR100/076/ERR10047676/ERR10047676_2.fastq.gzprimary200OKGenomicsEuropean Bioinformatics InstituteWallenberg Center for Molecular Medicine (WCMM) Department of Biomedical and Clinical Sciences (BKV) Division of Molecular Medicine and Virology (MMV) Faculty of Medicine and Health Sciences, Linkoping University, Linkoping, Swedenhttps://www.ebi.ac.uk/ena/browser/view/PRJEB55317ArrayExpressWnt/β-catenin signaling is a highly organized biochemical cascade that triggers a gene expression program in the signal-receiving cell. The Wnt/β-catenin-driven transcriptional response is involved in virtually all cellular processes during development, homeostasis, and its deregulation causes human disease. However, outstanding questions remain unanswered. A first question concerns cell-specificity: how this response is integrated into lineage-specific choices is still unknown. A second question concerns time: it is not known whether β-catenin associates with its targets simultaneously or in a time-dependent fashion. For instance, while TCF/LEF and other components of the Wnt transcriptional complex are constitutively associated with the chromatin, it is β-catenin arrival, upon Wnt induction, that launches target genes transcription. Therefore, discovering the dynamics of the genome-wide β-catenin binding pattern is required to unambiguously define the direct targets of Wnt signaling To address these questions, we realized a time-resolved atlas of β-catenin genome-wide occupancy in two human cell types, human embryonic kidney cells 293T (HEK293T) and human embryonic stem cells (hESCs). To this end, we treated HEK293T and hESCs with the GSK3 inhibitor/Wnt activator CHIR99021 (10 mM) for 3 days, and assessed β-catenin binding via CUT&RUN-LoV-U (Zambanini et al., 2022) 90 minutes, 4 hours, 24 hours and 3 days after the onset of the stimulation. This approach allowed us to establish that β-catenin repositions to different genomic loci along stimulation time, showing that a definition of Wnt target genes must take into account the time-dimension. Moreover, β-catenin physical targets are largely cell-type specific, as only a subset of them is present across the examined contexts.ENAWnt Signaling, Human Embryonic Kidney 293T, Canonical, Pathway, Canonical Wnt Pathway, 293tsA1609neo, Effects, Stem Cells, Longterm Effect, HEK 293 T, Canonical Wnt, Cell, Catenin, Long Term, 293T, Experiment, Catenin Protein, Signaling Pathway, Long Term Effects, Protein, Effect, Wnt Pathway, Human Embryonic, HEK293T, Wnt beta Catenin Signaling Pathway, 293-T, Longterm, Wnt beta-Catenin Signaling Pathway, hES cell line cell, Wnt Signaling Pathways, Long-Term, 293 T, Wnt, hESC, Longterm Effects, Hek 293T, hESC line cell, HEK-293T, Human Embryonic Stem Cell, Human Embryonic Stem, Catenin Proteins, Cells, Wnt Signalings, Signaling, Long-Term Effect, Canonical Wnt Pathways, Long-Term Effects, hESCs, HEK-293-T, activation.Wnt Signaling, Human Embryonic Kidney 293T, Canonical, Pathway, Canonical Wnt Pathway, 293tsA1609neo, Effects, Stem Cells, Longterm Effect, HEK 293 T, Canonical Wnt, Cell, Catenin, Long Term, 293T, Experiment, Catenin Protein, Signaling Pathway, Long Term Effects, Protein, Effect, Wnt Pathway, Human Embryonic, HEK293T, Wnt beta Catenin Signaling Pathway, 293-T, Longterm, Wnt beta-Catenin Signaling Pathway, hES cell line cell, Wnt Signaling Pathways, Long-Term, 293 T, Wnt, hESC, Longterm Effects, Hek 293T, hESC line cell, HEK-293T, Human Embryonic Stem Cell, Human Embryonic Stem, Catenin Proteins, Cells, Wnt Signalings, Signaling, Long-Term Effect, Canonical Wnt Pathways, Long-Term Effects, hESCs, HEK-293-T, activation.falseCUT&RUN experiment at four time points in HEK293T and hESC cells, assessing the time-resolved response of β-catenin genomic occupancy upon Wnt signaling activationCUT&RUN experiment at four time points in HEK293T and hESC cells, assessing the time-resolved response of β-catenin genomic occupancy upon Wnt signaling activation2022-09-302022-09-30PRJEB55317