Dimer formation via the homeodomain is required for function and specificity of Sex combs reduced in Drosophila

Developmental Biology
Dimitrios K PapadopoulosWalter J Gehring

Abstract

Hox transcription factors specify body segments along the anteroposterior axis of the embryo. Despite conservation of the homeodomain (HD), different Hox paralogs instruct remarkably different developmental fates. We have unexpectedly found that the Drosophila Sex combs reduced (Scr) protein dimerizes in vivo via the homeodomain, whereas its closest relative, Antennapedia (Antp), does not. Dimerization requires the conserved residue 19 in the ELEKEF motif of the HD and is facilitated by DNA binding. To study Scr dimerization in vivo, we generate a giant transcriptional puff in live salivary gland cells, consisting of a controllable multiple Scr-binding site of the fork head enhancer, and visualize Scr dimer formation upon specific DNA binding. Scr dimerization is required not only for transcriptional activation of the fork head gene but also for Scr homeotic function in the fly (formation of ectopic salivary glands, posterior transformations in the embryo and antenna-to-tarsus transformations). Finally, we attempt to attribute the differential behavior in dimer formation observed between Antp and Scr to diverse amino acid regions between the two proteins that account for dimerization in Scr versus non-dimerization in Antp. By c...Continue Reading

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Citations

Aug 5, 2015·Mechanisms of Development·Mehdi SaadaouiCorinne Maurel-Zaffran
Oct 16, 2015·Chromosoma·Thomas R Bürglin, Markus Affolter
Feb 12, 2014·Mechanisms of Development·Robert A DrewellJacqueline M Dresch
Oct 22, 2016·Current Opinion in Genetics & Development·Nicoletta Bobola, Samir Merabet
Mar 14, 2014·G3 : Genes - Genomes - Genetics·Lovesha Sivanantharajah, Anthony Percival-Smith
Nov 25, 2018·International Journal of Molecular Sciences·Zhaojiang GuoYoujun Zhang

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