Genomics

Dataset Information

102

A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus [RNA-Seq, HiC_C2C12, ChIP-Seq]


ABSTRACT: The binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here, we tested the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~15 CTCF binding sites, and located at the long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is invariant across evolution, tissues, and temporal dynamics of X-chromosome inactivation. We demonstrate that neither the deletion of this locus, nor the ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter TADs in a sex-, or allele-specific manner. In contrast, Firre’s deletion disrupts the chromatin super-loop formation of the inactive X-chromosome. Collectively, our findings suggest that apart from CTCF binding, additional mechanisms can play roles in establishing TAD boundary formation. Overall design: Hi-C in C2C12 mouse muscle cells, RNAseq in wildtype and Firre lncRNA knockout male and female mouse embryonic fibroblasts (MEFs), CTCF ChIP-seq in wildtype, Firre lncRNA kncokout and transgene MEFs

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

SUBMITTER: John Rinn 

PROVIDER: GSE104427 | GEO | 2018-02-12

REPOSITORIES: GEO

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Publications

A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus.

Barutcu A Rasim AR   Maass Philipp G PG   Lewandowski Jordan P JP   Weiner Catherine L CL   Rinn John L JL  

Nature communications 20180413 1


The binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here we test the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~ 15 CTCF binding sites and located at the long non-coding RNA (lncRNA  ...[more]

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