1. Developmental Biology
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The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila

  1. Katrin Domsch
  2. Julie Carnesecchi
  3. Vanessa Disela
  4. Jana Friedrich
  5. Nils Trost
  6. Olga Ermakova
  7. Maria Polychronidou
  8. Ingrid Lohmann  Is a corresponding author
  1. Centre for Organismal Studies, Heidelberg University, Germany
  2. EMBO, Germany
Research Article
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Cite this article as: eLife 2019;8:e42675 doi: 10.7554/eLife.42675

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).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Katrin Domsch

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Julie Carnesecchi

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Vanessa Disela

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jana Friedrich

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Nils Trost

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5171-018X
  6. Olga Ermakova

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Maria Polychronidou

    Molecular Systems Biology, EMBO, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Ingrid Lohmann

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    For correspondence
    ingrid.lohmann@cos.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0918-2758

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

  1. Bruce Edgar, University of Utah, United States

Publication history

  1. Received: October 8, 2018
  2. Accepted: April 30, 2019
  3. Accepted Manuscript published: May 3, 2019 (version 1)
  4. Version of Record published: May 13, 2019 (version 2)
  5. 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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