# Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development

Ian J. Donaldson
Shilu Amin
James Hensman, University of Lancaster
Eva Kutejova
Magnus Rattray, University of Manchester
Neil D. Lawrence, University of Sheffield
Andrew Hayes
Christopher M. Ward
Nicoletta Bobola

Nucleaic Acids Research 40, pp 3390-4001

#### 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–$\beta$-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.

  @Article{donaldson-genome12, title = {Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development}, journal = {Nucleaic Acids Research}, author = {Ian J. Donaldson and Shilu Amin and James Hensman and Eva Kutejova and Magnus Rattray and Neil D. Lawrence and Andrew Hayes and Christopher M. Ward and Nicoletta Bobola}, pages = {3390}, year = {2012}, volume = {40}, number = {9}, month = {00}, edit = {https://github.com/lawrennd//publications/edit/gh-pages/_posts/2012-01-01-donaldson-genome12.md}, url = {http://inverseprobability.com/publications/donaldson-genome12.html}, 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–$\beta$-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.}, key = {Donaldson-genome12}, doi = {10.1093/nar/gkr1240}, OPTgroup = {} }
 %T Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development %A Ian J. Donaldson and Shilu Amin and James Hensman and Eva Kutejova and Magnus Rattray and Neil D. Lawrence and Andrew Hayes and Christopher M. Ward and Nicoletta Bobola %B %C Nucleaic Acids Research %D %F donaldson-genome12 %J Nucleaic Acids Research %P 3390--4001 %R 10.1093/nar/gkr1240 %U http://inverseprobability.com/publications/donaldson-genome12.html %V 40 %N 9 %X 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–$\beta$-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. 
 TY - CPAPER TI - Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development AU - Ian J. Donaldson AU - Shilu Amin AU - James Hensman AU - Eva Kutejova AU - Magnus Rattray AU - Neil D. Lawrence AU - Andrew Hayes AU - Christopher M. Ward AU - Nicoletta Bobola PY - 2012/01/01 DA - 2012/01/01 ID - donaldson-genome12 SP - 3390 EP - 4001 DO - 10.1093/nar/gkr1240 UR - http://inverseprobability.com/publications/donaldson-genome12.html AB - 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–$\beta$-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. ER - 
 Donaldson, I.J., Amin, S., Hensman, J., Kutejova, E., Rattray, M., Lawrence, N.D., Hayes, A., Ward, C.M. & Bobola, N.. (2012). Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development. Nucleaic Acids Research 40(9):3390-4001