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Series GSE148368 Query DataSets for GSE148368
Status Public on Oct 18, 2021
Title Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary FOXA pioneer transcription factors (TFs) associate with primed enhancers in endodermal organ precursors. Using a human stem cell model of pancreas differentiation, we here discover that only a subset of pancreatic enhancers is FOXA-primed, whereas the majority is unprimed and engages FOXA upon lineage induction. Primed enhancers are enriched for signal-dependent TF motifs and harbor abundant and strong FOXA motifs. Unprimed enhancers harbor fewer, more degenerate FOXA motifs, and FOXA recruitment to unprimed but not primed enhancers requires pancreatic TFs. Strengthening FOXA motifs at an unprimed enhancer near NKX6.1 renders FOXA recruitment pancreatic TF-independent, induces priming, and broadens the NKX6.1 expression domain. We make analogous observations about FOXA binding during hepatic and lung development. Our findings suggest a dual role for FOXA in endodermal organ development: First, FOXA facilitate signal-dependent lineage initiation via enhancer priming, and second, FOXA enforce organ cell type-specific gene expression via indirect recruitment by lineage-specific TFs.
 
Overall design Anaysis of gene expression patterns by RNA-Seq, chromatin accessability by ATAC-Seq, and TF binding sites and histone marker distribution through ChIP-Seq performed within hESC-based models of endoderm differentiation. Effects of genetic deletion of FOXA1 and FOXA2 TFs on each aspect are examined in the context of pancreas induction.
 
Contributor(s) Geusz R, Sander M
Citation(s) 34789735
Submission date Apr 09, 2020
Last update date Dec 02, 2021
Contact name Maike Sander
E-mail(s) masander@ucsd.edu
Organization name UC San Diego
Street address 2880 Torrey Pines Scenic Dr.
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (107)
GSM4462965 Cyt49_GT.ChIP-Seq.FOXA1.replicate.1
GSM4462966 Cyt49_GT.ChIP-Seq.FOXA1.replicate.2
GSM4462967 Cyt49_GT.ChIP-Seq.FOXA2.replicate.1
Relations
BioProject PRJNA624086
SRA SRP255869

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Supplementary file Size Download File type/resource
GSE148368_RAW.tar 30.2 Gb (http)(custom) TAR (of BIGWIG, MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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