Scientific article
Open access

The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes

Published inGenes & development, vol. 31, no. 22, p. 2264-2281
Publication date2017-11-15
First online date2017-12-22

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos , we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed. The resulting progressive release in boundary effect triggered inter-TAD contacts, favored by the activity of the newly accessed enhancers. However, the boundary was highly resilient, and only a 400-kb deletion, including the whole-gene cluster, was eventually able to merge the neighboring TADs into a single structure. In this unified TAD, both proximal and distal limb enhancers nevertheless continued to work independently over a targeted transgenic reporter construct. We propose that the whole HoxD cluster is a dynamic TAD border and that the exact boundary position varies depending on both the transcriptional status and the developmental context.

  • CTCF
  • Hi-C
  • Hox
  • TAD
  • Genome architecture
  • Limb
Citation (ISO format)
RODRÍGUEZ-CARBALLO, Eddie et al. The <i>HoxD</i> cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes. In: Genes & development, 2017, vol. 31, n° 22, p. 2264–2281. doi: 10.1101/gad.307769.117
Main files (1)
Article (Published version)
ISSN of the journal0890-9369

Technical informations

Creation04/02/2024 4:23:07 PM
First validation04/26/2024 9:49:51 AM
Update time04/26/2024 9:49:51 AM
Status update04/26/2024 9:49:51 AM
Last indexation05/06/2024 6:28:22 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack