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.

Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development / Banerjee, K. K.; Saxena, M.; Kumar, N.; Chen, L.; Cavazza, A.; Toke, N. H.; O'Neill, N. K.; Madha, S.; Jadhav, U.; Verzi, M. P.; Shivdasani, R. A.. - In: GENES & DEVELOPMENT. - ISSN 0890-9369. - 32:21-22(2018), pp. 1430-1442. [10.1101/gad.318832.118]

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

Cavazza A.;
2018

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.
2018
32
21-22
1430
1442
Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development / Banerjee, K. K.; Saxena, M.; Kumar, N.; Chen, L.; Cavazza, A.; Toke, N. H.; O'Neill, N. K.; Madha, S.; Jadhav, U.; Verzi, M. P.; Shivdasani, R. A.. - In: GENES & DEVELOPMENT. - ISSN 0890-9369. - 32:21-22(2018), pp. 1430-1442. [10.1101/gad.318832.118]
Banerjee, K. K.; Saxena, M.; Kumar, N.; Chen, L.; Cavazza, A.; Toke, N. H.; O'Neill, N. K.; Madha, S.; Jadhav, U.; Verzi, M. P.; Shivdasani, R. A....espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1327195
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