Donaldson, I. J., Amin, S., Hensman, J. J. et al. (6 more authors) (2012) Genome-wide occupancy links Hoxa2 to Wnt-beta-catenin signaling in mouse embryonic development. Nucleic Acids Research , 40 (9). pp. 3990-4001. ISSN 0305-1048
Abstract
The regulation of gene expression is central to developmental programs and largely depends on the binding of sequence-specific transcription factors with cis-regulatory elements in the genome. Hox transcription factors specify the spatial coordinates of the body axis in all animals with bilateral symmetry, but a detailed knowledge of their molecular function in instructing cell fates is lacking. Here, we used chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) to identify Hoxa2 genomic locations in a time and space when it is actively instructing embryonic development in mouse. Our data reveals that Hoxa2 has large genome coverage and potentially regulates thousands of genes. Sequence analysis of Hoxa2-bound regions identifies high occurrence of two main classes of motifs, corresponding to Hox and Pbx–Hox recognition sequences. Examination of the binding targets of Hoxa2 faithfully captures the processes regulated by Hoxa2 during embryonic development; in addition, it uncovers a large cluster of potential targets involved in the Wnt-signaling pathway. In vivo examination of canonical Wnt–β-catenin signaling reveals activity specifically in Hoxa2 domain of expression, and this is undetectable in Hoxa2 mutant embryos. The comprehensive mapping of Hoxa2-binding sites provides a framework to study Hox regulatory networks in vertebrate developmental processes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | signal transduction; embryo; genes; genome; mice; transcription factor; embryologic development |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Dec 2016 15:44 |
Last Modified: | 12 Dec 2016 15:47 |
Published Version: | http://dx.doi.org/10.1093/nar/gkr1240 |
Status: | Published |
Publisher: | Oxford University Press (OUP): Policy C - Option B |
Refereed: | Yes |
Identification Number: | 10.1093/nar/gkr1240 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108795 |
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