Project description:We profiled the genome-wide occupancy of three tissue-specific transcription factors, HNF4A, CEBPA and FOXA1, as well as the genome-wide occurrence of the histone mark, H3K4me3 in the livers of two inbred parental mouse strains (C57BL/6J and CAST/EiJ) and their F1 crosses. We also included H3K27ac data generated from F1 hybrids as well as the profiling of HNF4A, CEBPA and FOXA1 in both CEBPA and HNF4a heterozygous knock-outs.
Project description:ChIP-seq for HNF4A, PPARGC1A and H3K27ac was performed in OE19 cells to identify genomic binding sites. Cells were treated with DMSO or 500 nM lapatinib for 48 hours.
Project description:We and others have suggested that pioneer activity–a transcription factor’s (TF’s) ability to bind and open inaccessible loci–is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci. Here we present a quantitative measure of pioneer activity that captures the relative difference in a TF’s ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure binding of doxycycline (dox) inducible TFs. For each location across the genome we determine a “dox50,” the concentration of dox required for a TF to reach half-maximal occupancy. We propose that the ratio of a TF’s average dox50 between ATAC-seq labeled inaccessible and accessible binding sites, its Δdox50, is a measure of its pioneer activity. We measured Δdox50’s for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has a smaller Δdox50 than FOXA1, suggesting that HNF4A has stronger pioneer activity than FOXA1. We further show that FOXA1 binding sites with more copies of its motif have a lower Δdox50, suggesting that strong motif content may compensate for weak pioneer activity. Our results suggest that Δdox50s, or other similar measures that assess the difference in TF affinity for inaccessible and accessible DNA, are reasonable measures of pioneer activity.
Project description:This study aims to investigate the DNA methylation patterns at transcription factor binding regions and their evolutionary conservation with respect to binding activity divergence. We combined newly generated bisulfite-sequencing experiments in livers of five mammals (human, macaque, mouse, rat and dog) and matched publicly available ChIP-sequencing data for five transcription factors (CEBPA, HNF4a, CTCF, ONECUT1 and FOXA1). To study the chromatin contexts of TF binding subjected to distinct evolutionary pressures, we integrated publicly available active promoter, active enhancer and primed enhancer calls determined by profiling genome wide patterns of H3K27ac, H3K4me3 and H3K4me1.
Project description:This study aims to study genome wide location of HNF4a, FoxA1 and CEBPA in wild type rat liver. Please note that all raw data files for this study were replaced with new versions on 12 March 2014 because the previous versions are corrupted. The corrupted files are associated with ENA run accessions ERR215698 to ERR215705 and should not be used. The correct files are associated with ENA run accessions ERR458085 to ERR458092.
Project description:In this study, we showed that activated Wnt/β-catenin signaling suppressed HAL and ARG1, genes associated with cellular metabolism, via CEBPA and FOXA1 transcription factors. In contrast, inhibition of the Wnt signaling pathway increased HAL and ARG1, resulting in decreased intracellular levels of histidine and arginine in liver cancer cells. These data gain an insight into a new role of the Wnt signaling pathway in amino acid metabolism in liver cancer.
Project description:ChIP-seqs of BMAL1, HNF4A, FOXA2, H3K4me1, and H3K27ac were profiled in mouse liver tissues upon Hnf4a or Bmal1 knockout. BMAL1, H3K4me1, and H3K27ac ChIP-seq were profiled in U2OS cells ectopically expressing HNF4A.