The Hox Transcription Factor Ubx Stabilizes Lineage Commitment by Suppressing Cellular Plasticity in

Overview

Journal Elife

Specialty Biology

Date 2019 May 4

PMID 31050646

Citations 16

Authors

Katrin Domsch

Julie Carnesecchi

Vanessa Disela

Jana Friedrich

Nils Trost

Olga Ermakova

Maria Polychronidou

Ingrid Lohmann

Affiliations

Soon will be listed here.

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 (Ubx), 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.

Citing Articles

Comprehensive Predictions of Mef2-Mediated Chromatin Loops, Which May Inhibit Ubx Binding by Blocking Low-Affinity Binding Sites.

Domsch K J Dev Biol. 2024; 12(4).

PMID: 39728086 PMC: 11678716. DOI: 10.3390/jdb12040033.

Canalizing cell fate by transcriptional repression.

Lim B, Domsch K, Mall M, Lohmann I Mol Syst Biol. 2024; 20(3):144-161.

PMID: 38302581 PMC: 10912439. DOI: 10.1038/s44320-024-00014-z.

Micromanagement of Post-Embryonic Development by Hox Genes.

Buffry A, McGregor A J Dev Biol. 2022; 10(1).

PMID: 35225966 PMC: 8883937. DOI: 10.3390/jdb10010013.

Single-cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos.

Velten J, Gao X, van Nierop Y Sanchez P, Domsch K, Agarwal R, Bognar L Mol Syst Biol. 2022; 18(3):e10255.

PMID: 35225419 PMC: 8883443. DOI: 10.15252/msb.202110255.

An Evolutionary Perspective on Hox Binding Site Preferences in Two Different Tissues.

Folkendt L, Lohmann I, Domsch K J Dev Biol. 2021; 9(4).

PMID: 34940504 PMC: 8705983. DOI: 10.3390/jdb9040057.

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