Cdx is crucial for the timing mechanism driving colinear Hox activation and defines a trunk segment in the Hox cluster topology

TY - JOUR

T1 - Cdx is crucial for the timing mechanism driving colinear Hox activation and defines a trunk segment in the Hox cluster topology

AU - Neijts, Roel

AU - Amin, Shilu

AU - van Rooijen, Carina

AU - Deschamps, Jacqueline

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/12/29

Y1 - 2016/12/29

N2 - Cdx and Hox transcription factors are important regulators of axial patterning and are required for tissue generation along the vertebrate body axis. Cdx genes have been demonstrated to act upstream of Hox genes in midgestation embryos. Here, we investigate the role of Cdx transcription factors in the gradual colinear activation of the Hox clusters. We found that Hox temporally colinear expression is severely affected in epiblast stem cells derived from Cdx null embryos. We demonstrate that after initiation of 3' Hox gene transcription, Cdx activity is crucial for H3K27ac deposition and for accessibility of cis-regulatory elements around the central - or 'trunk' - Hox genes. We thereby identify a Cdx-responsive segment of HoxA, immediately 5' to the recently defined regulatory domain orchestrating initial transcription of the first Hox gene. We propose that this partition of HoxA into a Wnt-driven 3' part and the newly found Cdx-dependent middle segment of the cluster, forms a structural fundament of Hox colinearity of expression. Subsequently to initial Wnt-induced activation of 3' Hox genes, Cdx transcription factors would act as crucial effectors for activating central Hox genes, until the last gene of the cluster arrests the process.

AB - Cdx and Hox transcription factors are important regulators of axial patterning and are required for tissue generation along the vertebrate body axis. Cdx genes have been demonstrated to act upstream of Hox genes in midgestation embryos. Here, we investigate the role of Cdx transcription factors in the gradual colinear activation of the Hox clusters. We found that Hox temporally colinear expression is severely affected in epiblast stem cells derived from Cdx null embryos. We demonstrate that after initiation of 3' Hox gene transcription, Cdx activity is crucial for H3K27ac deposition and for accessibility of cis-regulatory elements around the central - or 'trunk' - Hox genes. We thereby identify a Cdx-responsive segment of HoxA, immediately 5' to the recently defined regulatory domain orchestrating initial transcription of the first Hox gene. We propose that this partition of HoxA into a Wnt-driven 3' part and the newly found Cdx-dependent middle segment of the cluster, forms a structural fundament of Hox colinearity of expression. Subsequently to initial Wnt-induced activation of 3' Hox genes, Cdx transcription factors would act as crucial effectors for activating central Hox genes, until the last gene of the cluster arrests the process.

U2 - 10.1016/j.ydbio.2016.12.024

DO - 10.1016/j.ydbio.2016.12.024

M3 - Article

C2 - 28041967

SN - 0012-1606

JO - Developmental Biology

JF - Developmental Biology

ER -