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DNMT1 interacts with the developmental transcriptional repressor HESX1

Sajedi, E; Gaston-Massuet, C; Andoniadou, CL; Signore, M; Hurd, PJ; Dattani, M; Martinez-Barbera, JP; (2008) DNMT1 interacts with the developmental transcriptional repressor HESX1. BBA-MOL CELL RES , 1783 (1) 131 - 143. 10.1016/j.bbamcr.2007.08.010. Gold open access

Abstract

Hesx1 is a highly conserved homeobox gene present in vertebrates, but absent from invertebrates. Gene targeting experiments in mice have shown that this transcriptional repressor is required for normal forebrain and pituitary development. In humans, mutations in HESX1 impairing either its repressing activity or DNA binding properties lead to a comparable phenotype to that observed in Hesx1 deficient mice. In an attempt to gain insights into the molecular function of HESX1, we have performed a yeast two-hybrid screen and identified DNA methyltransferase 1 (DNMT1) as a HESX1 binding protein. We show that Dnmt1 is co-expressed with Hesx1 within the anterior forebrain and in the developing Ratlike's pouch. Mapping of the interacting regions indicates that the entire HESX1 protein is required to establish binding to a portion of the N-terminus of DNMT1 and its catalytic domain in the C-terminus. The HESX1-DNMT1 complexes can be immunoprecipitated in cells and co-localise in the nucleus. These results establish a link between HESX1 and DNMT1 and suggest a novel mechanism for the repressing properties of HESX1. (C) 2007 Elsevier B.V. All rights reserved.

Type: Article
Title: DNMT1 interacts with the developmental transcriptional repressor HESX1
Open access status: An open access publication
DOI: 10.1016/j.bbamcr.2007.08.010
Publisher version: http://ukpmc.ac.uk/abstract/MED/17931718
Keywords: DNA methylation, repression, homeobox, forebrain, pituitary, mouse, SEPTO-OPTIC DYSPLASIA, ANTERIOR NEURAL PLATE, HOMEOBOX GENE HESX1, DNA METHYLTRANSFERASE, PRIMITIVE ENDODERM, RATHKES POUCH, MOUSE EMBRYO, PITUITARY, COMPLEX, MUTATIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Genetics and Genomic Medicine Prog
UCL > Provost and Vice Provost Offices > VP Health
UCL > Provost and Vice Provost Offices > VP Health > Translational Research Office
URI: http://discovery.ucl.ac.uk/id/eprint/99376
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