Role of HOX genes and regula1on of gene expression Rob White - PowerPoint PPT Presentation

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Role of HOX genes and regula1on of gene expression Rob White Department of Physiology, Development and Neuroscience University of Cambridge Hox Mutants - Homeo1c phenotypes in Drosophila Wild type Loss of Ubx Hox gene func1on Wild type

Role of HOX genes and regula1on of gene expression Rob White Department of Physiology, Development and Neuroscience University of Cambridge
Hox Mutants - Homeo1c phenotypes in Drosophila Wild type Loss of Ubx Hox gene func1on Wild type Ectopic mis-expression of Hox gene Antp
Conserva1on of Hox genes and their expression
Hox gene complexes
Hox genes paGern the anterior-posterior axis From Kosman et al (2004)
Hox gene expression - a developmental code
The Hox Code - paGerning the mammalian axial skeleton McIntyre et al (2007) Development 134: 2981-2989
Hox homeodomain DNA binding and Hox specificity
Hox cofactors Drosophila Extraden1cle and Homothorax Vertebrate Pbx and Meis proteins Slattery et al (2011) Cell 147,1270-82
Hox proteins binds to thousands of sites in the Drosophila genome Ubx Ubx + Exd/Hth Sites in Genome: Ubx 8,672 Ubx + Exd/Hth 11,698 Beh et al (2016) Epigene1cs and Chroma1n 9:1
Master regulators or Micromanagers? Hox gene Hox gene High level regulators High level regulators Low level regulators Low level regulators Realisator genes Realisator genes
Hox target genes Choo et al (2011) PLoS ONE 6:e14778
Hox genes control motor neuron iden1ty and circuits Philippidou and Dasen (2013) Neuron 80; 12-34
Hox genes are re-used in Proximal-Distal paGerning in vertebrate limbs Pineault and Wellick (2014) Curr. Osteoporos Rep 12:420-427 Zakany and Duboule (2007) Curr Op Gen and Dev 17:359-366
Hox genes micromanaging cell processes Cell shape Differen1a1on Cell migra1on Hox genes Cell prolifera1on Cell death Cell adhesion
Enhancer-Promoter Loops in Gene Regula1on Allen and Taatjes (2015) Nature Reviews M C B 16, 155–166
Long-range Regulatory Elements
Topologically-Associated Domains (TADs)
The domain organisa1on of the genome TADs – Topologically Associated Domains Dixon et al (2012) Nature 485: 376-380 Rao et al (2014) Cell 159: 1665-1680 Sanborn et al (2015) PNAS : E6456-6465
Domain organisa1on and HoxD regula1on Lonfat and Duboule (2015) FEBSLeGs 589: 2869-2876
Enhancer range is delimited by domain boundaries Lupianez et al (2015) Cell 161:1012-1025
Domain Structure : Polytene Chromosomes Balbiani (1881)

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