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Genes Dev. 2018 Nov 1;32(21-22):1430-1442. doi: 10.1101/gad.318832.118. Epub 2018 Oct 26.

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

Author information

1
Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
2
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
3
Department of Genetics, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA.
4
Cancer Institute of New Jersey, Piscataway, New Jersey 08854, USA.
5
Human Genetics Institute of New Jersey, Piscataway, New Jersey 08854, USA.
6
Harvard Stem Cell Institute, Cambridge, Massachusetts 02139, USA.
#
Contributed equally

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.

KEYWORDS:

chromatin plasticity; developmental competence; developmental plasticity; fate determination; homeodomain transcription factors; lineage commitment; tissue specification

PMID:
30366903
PMCID:
PMC6217732
[Available on 2019-05-01]
DOI:
10.1101/gad.318832.118
[Indexed for MEDLINE]

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