Dissecting the functional specificities of two Hox proteins.

Genes & Development
Rohit JoshiRichard S Mann

Abstract

Hox proteins frequently select and regulate their specific target genes with the help of cofactors like Extradenticle (Exd) and Homothorax (Hth). For the Drosophila Hox protein Sex combs reduced (Scr), Exd has been shown to position a normally unstructured portion of Scr so that two basic amino acid side chains can insert into the minor groove of an Scr-specific DNA-binding site. Here we provide evidence that another Drosophila Hox protein, Deformed (Dfd), uses a very similar mechanism to achieve specificity in vivo, thus generalizing this mechanism. Furthermore, we show that subtle differences in the way Dfd and Scr recognize their specific binding sites, in conjunction with non-DNA-binding domains, influence whether the target gene is transcriptionally activated or repressed. These results suggest that the interaction between these DNA-binding proteins and the DNA-binding site determines the architecture of the Hox-cofactor-DNA ternary complex, which in turn determines whether the complex recruits coactivators or corepressors.

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Citations

Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kathryn J BrayerGünter P Wagner
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Katherine M LelliRichard S Mann
Nov 17, 2011·Genes & Development·Barbara NoroRichard S Mann
Aug 21, 2013·PLoS Computational Biology·Volodymyr BabinCeleste Sagui
Mar 7, 2014·Frontiers in Zoology·Ralf JanssenGraham E Budd
Jun 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dimitrios K PapadopoulosWalter J Gehring
Sep 1, 2012·Annual Review of Genetics·Katherine M LelliRichard S Mann
Dec 3, 2014·Developmental Biology·Lovesha Sivanantharajah, Anthony Percival-Smith
Aug 5, 2015·Mechanisms of Development·Mehdi SaadaouiCorinne Maurel-Zaffran
Sep 27, 2015·Mechanisms of Development·Raviranjan KumarRohit Joshi
Mar 19, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Terence D CapelliniLicia Selleri
Mar 14, 2012·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Mala MisraCynthia Lance-Jones
Jul 12, 2012·The EMBO Journal·Sebastian SorgeIngrid Lohmann
Apr 14, 2016·Trends in Genetics : TIG·Samir Merabet, Richard S Mann
Oct 14, 2014·Seminars in Cell & Developmental Biology·A Keith DunkerChristopher J Oldfield
Nov 17, 2016·Development Genes and Evolution·Anthony Percival-Smith
Aug 11, 2019·Nature Communications·Carlos Sánchez-HiguerasJames C-G Hombría
Jul 28, 2016·G3 : Genes - Genomes - Genetics·Alisha V JohnPatricia J Wittkopp
Mar 26, 2015·Development·René RezsohazyYacine Graba
Jun 23, 2012·Development·Isabel GuerreiroMoisés Mallo
Jun 3, 2021·International Journal of Molecular Sciences·Maria Rita GulottaAndrea Brancale
Jun 9, 2021·Developmental Biology·Bony De Kumar, Diane C Darland

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