Project description:We investigated which genomic regions the transcription factor Hnf4a, ectopically introduced to induce hepatocyte-like cells (iHepCs) from MEFs through direct reprogramming, binds to in iHepCs.
Project description:We optimized the epigenomic profiling technology ChIL-seq for tissue. We confirmed the "ChIL for tissue" has sufficient sensitivity, specificity and reproducibility, in identification of enhancers, transcription factors, transcriptional activation genes in a single-thin-section of tissues.
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:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Examination of PIC, H3k4me3, Ctcf and Hnf4a occupancy in wild-type and Taf4-/- livers by deep sequencing
Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes.
Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes.
Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. RNA profiles in wild-type and Taf4-/- livers by deep sequencing
Project description:HNF4A mRNA cycles over the coure of 24 h. To understand whether the chromatin binding of the transcription factor is also rhythmic, we performed ChIP-seq for HNF4A using mouse liver samples of ZT4 and ZT16. By analysing this dataset, we conclude that HNF4A binds chromatin much more robustly during the evening ( at ZT16).