Genomics

Dataset Information

103

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


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: ChIP analysis of CTCF, SMC1, RAD21 and H3K27ac E12.5 limb tissues from Wt or serial HoxD-deleted alleles

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Eddie Rodríguez-Carballo  

PROVIDER: GSE101714 | GEO | 2017-12-22

SECONDARY ACCESSION(S): PRJNA395245

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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