# Oxford BioDynamics plc – Dissecting super-enhancer hierarchy based on chromatin interactions

- Link: https://www.directorstalkinterviews.com/oxford-biodynamics-plc-dissecting-super-enhancer-hierarchy-based-chromatin-interactions/412748956
- Published: 2018-04-06T10:29:25+01:00
- Author: Giles Arbor

Recent studies have highlighted super-enhancers (SEs) as important regulatory elements
for gene expression, but their intrinsic properties remain incompletely characterized.
Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant
fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers.

Here we develop an approach to dissect the compositional organization of SEs based
on long-range chromatin interactions. We find that a subset of SEs exhibits a hierarchical
structure, and hub enhancers within hierarchical SEs play distinct roles in chromatin
organization and gene activation. Our findings also identify a critical role for
CTCF in organizing the structural (and hence functional) hierarchy of SEs.

**DirectorsTalk caught up with Alexandre Akoulitchev the CEO of Oxford BioDynamics
plc (LON:OBD) for his thoughts on this paper:**

> Wonderfull paper in Nature Communications from Dana-Farber Cancer Institute, Harvard
> Medical School, Howard Hughs Medical Institute and several other leading Institutions
> in US.
> Very encouraging to see that the field of structure-function of genome 3D architecture
> is maturing and bringing new insights into complexities and regulatory context
> of genome regulation.
> When analysed in cell lines a broad network of almost 30, 000 enhancers, generally
> implicated in transcriptional regulation of gene promoters, shows intricate hierarchical
> organisation. At the top of that pyramid are super-enhancers with the properties
> of hierarchical hubs – just less then 2% of all enhancer network. Those hubs show
> clear evidence for protein machinery of long range chromosomal interactions – 
> chromosome conformation signatures, and evolutionary high pressure for enrichment
> of genetic variants – SNPs and eQTLs, associated with diseases, critical effects
> on gene expression (very elegant CRISPR interference and editing experiments) 
> and control of cellular phenotype.
> Fascinating to see, that subset of blood based eQTLs is most significantly associated
> with the hubs, when compared with any other eQTLS.
> This systematic study gives further scientific support to technological approaches
> developed and deployed today by Oxford BioDynamics plc : blood-based selective
> monitoring of genome architecture through the hubs of long range chromosome conformation
> signatures have been delivering robust and validated stratification signatures
> in patient patient cohorts for several diseases indications.

The article in reference can be found here: https://www.nature.com/articles/s41467-
018-03279-9

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