The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila

Abstract
Data availability
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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

(2019) All sequencing data for The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila
NCBI Gene Expression Omnibus, GSE121754.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121754
(2019) RNA-Seq data for The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila
NCBI Gene Expression Omnibus, GSE121670.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121670
(2019) ChIP-Seq data for The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila
NCBI Gene Expression Omnibus, GSE121752.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121752

The following previously published data sets were used

1. Erceg
2. Pakozdi
3. Marco-Ferreres
4. Ghavi-Helm
5. Girardot
6. Bracken
7. Furlong
(2017) Time course Pho/dSfmbt Chromatin Immunoprecipitation on Drosophila melanogaster embryos during embryogenesis
European Nucleotide Archive, ERR1358767-ERR1358777.

http://www.ebi.ac.uk/ena/data/view/ERR1358767-ERR1358777
1. Jin H
2. Stojnic R
3. Adryan B
4. Ozdemir A
5. Stathopoulos A
6. Frasch M
(2013) Genome-wide Tinman binding sites in early and late Drosophila embryos
NCBI Gene Expression Omnibus,GSE41628.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41628
(2006) A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development
ArrayExpress, E-TABM-56.

https://www.ebi.ac.uk/arrayexpress/experiments/E-TABM-56/

Article and author information

Author details

Katrin Domsch

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Julie Carnesecchi

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Vanessa Disela

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Jana Friedrich

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Nils Trost

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5171-018X
Olga Ermakova

Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Maria Polychronidou

Molecular Systems Biology, EMBO, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.