Genomics

Dataset Information

108

A TAD boundary at the HoxD locus segregates opposing limb regulatory landscapes and their target genes [Hi-C]


ABSTRACT: The mammalian HoxD cluster is positioned at the boundary between two topologically associating domains (TADs), each of them matching a distinct, enhancer-rich regulatory landscape. During limb development, the telomeric TAD controls the early phase of Hoxd gene transcription in future forearm cells, whereas the centromeric TAD subsequently regulates transcription of more posterior Hoxd genes in presumptive digit cells. The TAD boundary is essential as it prevents the terminal Hoxd13 gene to respond to potent forearm enhancers, thereby allowing the formation of proper proximal limb structures. Here we apply chromosome conformation capture onto embryonic proximal and distal limb bud cells micro-dissected from a set of nested deletions involving part- or all- of this boundary region to try to understand the nature and function of this CTCF- and cohesin-rich DNA region. We document a progressive release of the boundary effect, allowing for inter-TAD contacts to be established, which were favoured by the functional status of the newly accessed enhancers. However, the boundary was highly resilient and only a 400kb large deletion including the whole gene cluster was eventually able to merge the two neighbouring TADs into a single structure. We propose that the whole HoxD cluster is a dynamic transcriptional boundary, showing slight variations depending on both the transcriptional status and the ontogenetic context Overall design: Hi-C datasets of E12.5 limb tissues (distal or proximal forelimbs and hindlimbs) of Wt or serial HoxD-deleted alleles -delHoxd(1-13d9)lac and delHoxd(attP-Rel5)d9lac as well as the reanalysis of the CH12 dataset from Rao et al. 2014 (GSE63525, GSM15516333 to GSM15516347 = SRR1658716 to SRR1658730) and mESC dataset from Dixon et al. 2012 (GSE35156, GSM862720 = SRR443883 to SRR443885 and GSM862721 = SRR400251 to SRR400256) on mm10.

REANALYSIS of: GSE51334GSE63525

INSTRUMENT(S): Illumina HiSeq 4000 (Mus musculus)

SUBMITTER: Eddie Rodríguez-Carballo  

PROVIDER: GSE101715 | GEO | 2017-12-22

SECONDARY ACCESSION(S): PRJNA395244

REPOSITORIES: GEO

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Publications

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

Rodríguez-Carballo Eddie E   Lopez-Delisle Lucille L   Zhan Ye Y   Fabre Pierre J PJ   Beccari Leonardo L   El-Idrissi Imane I   Huynh Thi Hanh Nguyen THN   Ozadam Hakan H   Dekker Job J   Duboule Denis D  

Genes & development 20171101 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 natu  ...[more]

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