Journal
DEVELOPMENT
Volume 146, Issue 19, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.179432
Keywords
HNF4 transcription factors; Developing intestine; Maturation; Chromatin
Categories
Funding
- National Cancer Institute [R01CA190558]
- Intestinal Stem Cell Consortium from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Allergy and Infectious Diseases (NIAID) [U01 DK103141]
- Sequencing Facility of the Rutgers Cancer Institute of New Jersey - National Cancer Institute [P30CA072720]
- University of Michigan Center for Gastrointestinal Research (UMCGR) [NIDDK 5P30DK034933]
- New Jersey Commission on Cancer Research grant [DFHS18PPC051]
- MacMillan Summer Undergraduate Research Fellowships
Ask authors/readers for more resources
As embryos mature, cells undergo remarkable transitions that are accompanied by shifts in transcription factor regulatory networks. Mechanisms driving developmental transitions are incompletely understood. The embryonic intestine transitions from a rapidly proliferating tube with pseudostratified epithelium prior to murine embryonic day (E) 14.5 to an exquisitely folded columnar epithelium in fetal stages. We sought to identify factors driving mouse fetal intestinal maturation by mining chromatin accessibility data for transcription factor motifs. ATAC-seq accessible regions shift during tissue maturation, with CDX2 transcription factor motifs abundant at chromatin-accessible regions of the embryo. Hepatocyte nuclear factor 4 (HNF4) transcription factor motifs are the most abundant in the fetal stages (>E16.5). Genetic inactivation of Hnf4a and its paralog Hnf4g revealed that HNF4 factors are redundantly required for fetal maturation. CDX2 binds to and activates Hnf4 gene loci to elevate HNF4 expression at fetal stages. HNF4 and CDX2 transcription factors then occupy shared genomic regulatory sites to promote chromatin accessibility and gene expression in the maturing intestine. Thus, HNF4 paralogs are key components of an intestinal transcription factor network shift during the embryonic to fetal transition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available