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Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development

Banerjee, KK; Saxena, M; Kumar, N; Chen, L; Cavazza, A; Toke, NH; O'Neill, NK; ... Shivdasani, RA; + view all (2018) Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development. Genes and Development , 32 (21-22) pp. 1430-1442. 10.1101/gad.318832.118. Green open access

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Abstract

After acquiring competence for selected cell fates, embryonic primordia may remain plastic for variable periods before tissue identity is irrevocably determined (commitment). We investigated the chromatin basis for these developmental milestones in mouse endoderm, a tissue with recognizable rostro-caudal patterning and transcription factor (TF)-dependent interim plasticity. Foregut-specific enhancers are as accessible and active in early midgut as in foregut endoderm, and intestinal enhancers and identity are established only after ectopic cis-regulatory elements are decommissioned. Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Thus, midgut endoderm is primed for heterologous cell fates, and TFs act on a background of shifting chromatin access to determine intestinal at the expense of foregut identity. Similar principles likely govern other fate commitments.

Type: Article
Title: Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/gad.318832.118
Publisher version: https://doi.org/10.1101/gad.318832.118
Language: English
Additional information: © 2018 Banerjee et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms. xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Keywords: developmental competence; fate determination; tissue specification; lineage commitment; developmental plasticity; chromatin plasticity; homeodomain transcription factors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10077591
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