title: Polarized regulatory landscape and Wnt responsiveness underlie Hox activation in embryos.
abstract: Sequential 3'-to-5' activation of the Hox gene clusters in early embryos is a most fascinating issue in developmental biology. Neither the trigger nor the regulatory elements involved in the transcriptional initiation of the 3'-most Hox genes have been unraveled in any organism. We demonstrate that a series of enhancers, some of which are Wnt-dependent, is located within a HoxA 3' subtopologically associated domain (subTAD). This subTAD forms the structural basis for multiple layers of 3'-polarized features, including DNA accessibility and enhancer activation. Deletion of the cassette of Wnt-dependent enhancers proves its crucial role in initial transcription of HoxA at the 3' side of the cluster.
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Roel
authors.identifier: http://orcid.org/0000-0003-2549-1777
authors.initials: R
authors.lastname: Neijts
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Shilu
authors.initials: S
authors.lastname: Amin
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Carina
authors.initials: C
authors.lastname: van Rooijen
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Tan
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Menno P
authors.initials: MP
authors.lastname: Creyghton
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Deschamps
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015533:Transcriptional Activation / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D051153:Wnt Proteins; C088144:HoxA protein
keywords: DNA accessibility; Hox regulation; chromatin conformation; developmental enhancers; regulatory landscapes