The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila
- Centre for Organismal Studies, Heidelberg University, Germany
- EMBO, Germany
Abstract
During development cells become restricted in their differentiation potential by repressing alternative cell fates, and the Polycomb complex plays a crucial role in this process. However, how alternative fate genes are lineage-specifically silenced is unclear. We studied Ultrabithorax, a multi-lineage transcription factor of the Hox class, in two tissue lineages using sorted nuclei and interfered with Ubx in mesodermal cells. We find that depletion of Ubx leads to the de-repression of genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by retaining the Polycomb Group protein Pleiohomeotic at Ubx targeted genomic regions, thereby stabilizing repressive chromatin marks in a lineage-dependent manner. Our study demonstrates that Ubx stabilizes lineage choice by suppressing the multipotency encoded in the genome via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it could set a block to transdifferentiation in adult cells.
Data availability
Sequencing data have been deposited in GEO: GSE121754 (all), GSE121670 (RNA-Seq) & GSE121752 (ChIP-Seq).
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Time course Pho/dSfmbt Chromatin Immunoprecipitation on Drosophila melanogaster embryos during embryogenesisEuropean Nucleotide Archive, ERR1358767-ERR1358777.
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Genome-wide Tinman binding sites in early and late Drosophila embryosNCBI Gene Expression Omnibus,GSE41628.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (LO 844 8/1)
- Ingrid Lohmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bruce Edgar, University of Utah, United States
Version history
- Received: October 8, 2018
- Accepted: April 30, 2019
- Accepted Manuscript published: May 3, 2019 (version 1)
- Version of Record published: May 13, 2019 (version 2)
- Version of Record updated: May 16, 2019 (version 3)
Copyright
© 2019, Domsch et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila
eLife 8:e42675.
https://doi.org/10.7554/eLife.42675
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