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

Ian J. Donaldson, Shilu Amin, James Hensman, Eva Kutejova, Magnus Rattray, Neil D. Lawrence, Andrew Hayes, Christopher M. Ward, Nicoletta Bobola
Nucleaic Acids Research, 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-$eta$-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
@Article{Donaldson-genome12, title = {Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development}, author = {Donaldson, Ian J. and Amin, Shilu and Hensman, James and Kutejova, Eva and Rattray, Magnus and Lawrence, Neil D. and Hayes, Andrew and Ward, Christopher M. and Bobola, Nicoletta}, journal = {Nucleaic Acids Research}, pages = {3390--4001}, year = {2012}, volume = {40}, number = {9}, doi = {10.1093/nar/gkr1240}, 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-$eta$-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 Journal Article %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 %J Nucleaic Acids Research %D 2012 %F Donaldson-genome12 %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-$eta$-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 - JOUR 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 DA - 2012/01/02 ID - Donaldson-genome12 VL - 40 IS - 9 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-$eta$-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.. (2012). Genome-wide occupancy links Hoxa2 to Wnt-$\beta$-catenin signaling in mouse embryonic development. Nucleaic Acids Research 40(9):3390-4001 doi:10.1093/nar/gkr1240 Available from http://inverseprobability.com/publications/donaldson-genome12.html.

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