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

Ian J. Donaldson, Shilu Amin, James Hensman, Eva Kutejova, Magnus RattrayNeil D. Lawrence, Andrew Hayes, Christopher M. Ward, Nicoletta Bobola
,  40(9):3390-4001, 2012.

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.

Cite this Paper


BibTeX
@InProceedings{pmlr-v-donaldson-genome12, title = {Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development}, 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--4001}, year = {}, editor = {}, volume = {40}, number = {9}, 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.} }
Endnote
%0 Conference Paper %T Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development %A Ian J. Donaldson %A Shilu Amin %A James Hensman %A Eva Kutejova %A Magnus Rattray %A Neil D. Lawrence %A Andrew Hayes %A Christopher M. Ward %A Nicoletta Bobola %B %C Proceedings of Machine Learning Research %D %E %F pmlr-v-donaldson-genome12 %I PMLR %J Proceedings of Machine Learning Research %P 3390--4001 %R 10.1093/nar/gkr1240 %U http://inverseprobability.com %V %N 9 %W PMLR %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.
RIS
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 BT - PY - DA - ED - ID - pmlr-v-donaldson-genome12 PB - PMLR SP - 3390 DP - PMLR EP - 4001 DO - 10.1093/nar/gkr1240 L1 - 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 -
APA
Donaldson, I.J., Amin, S., Hensman, J., Kutejova, E., Rattray, M., Lawrence, N.D., Hayes, A., Ward, C.M. & Bobola, N.. (). Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development. , in PMLR (9):3390-4001

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