Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Hoxa2 selectively enhances meis binding to change a branchial arch ground state
AU - Amin, Shilu
AU - Donaldson, Ian J.
AU - Zannino, Denise A.
AU - Hensman, James
AU - Rattray, Magnus
AU - Losa, Marta
AU - Spitz, François
AU - Ladam, Franck
AU - Sagerström, Charles
AU - Bobola, Nicoletta
PY - 2015/2/9
Y1 - 2015/2/9
N2 - Hox transcription factors (TFs) are essential for vertebrate development, but how these evolutionary conserved proteins function invivo remains unclear. Because Hox proteins have notoriously low binding specificity, they are believed to bind with cofactors, mainly homeodomain TFs Pbx and Meis, to select their specific targets. We mapped binding of Meis, Pbx, and Hoxa2 in the branchial arches, a series of segments in the developing vertebrate head. Meis occupancy is largely similar in Hox-positive and -negative arches. Hoxa2, which specifies second arch (IIBA) identity, recognizes a subset of Meis preboundsites that contain Hox motifs. Importantly, at these sites Meis binding is strongly increased. This enhanced Meis binding coincides with active enhancers, which are linked to genes highly expressed in the IIBA and regulated by Hoxa2. These findings show that Hoxa2 operates as a tissue-specific cofactor, enhancing Meis binding to specific sites that provide the IIBA with its anatomical identity.
AB - Hox transcription factors (TFs) are essential for vertebrate development, but how these evolutionary conserved proteins function invivo remains unclear. Because Hox proteins have notoriously low binding specificity, they are believed to bind with cofactors, mainly homeodomain TFs Pbx and Meis, to select their specific targets. We mapped binding of Meis, Pbx, and Hoxa2 in the branchial arches, a series of segments in the developing vertebrate head. Meis occupancy is largely similar in Hox-positive and -negative arches. Hoxa2, which specifies second arch (IIBA) identity, recognizes a subset of Meis preboundsites that contain Hox motifs. Importantly, at these sites Meis binding is strongly increased. This enhanced Meis binding coincides with active enhancers, which are linked to genes highly expressed in the IIBA and regulated by Hoxa2. These findings show that Hoxa2 operates as a tissue-specific cofactor, enhancing Meis binding to specific sites that provide the IIBA with its anatomical identity.
U2 - 10.1016/j.devcel.2014.12.024
DO - 10.1016/j.devcel.2014.12.024
M3 - Journal article
C2 - 25640223
AN - SCOPUS:84922804680
VL - 32
SP - 265
EP - 277
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 3
ER -