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The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Stefan Schoenfelder1, Mayra Furlan-Magaril1, Borbala Mifsud2
1Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom;
Genome Research
|March 11, 2015
Summary
Researchers mapped long-range regulatory elements to target genes genome-wide using a novel Hi-C enrichment method. This catalog reveals complex spatial gene regulation networks critical for development.
Area of Science:
- Genomics
- Epigenetics
- Gene Regulation
Background:
- Mammalian genomes contain numerous regulatory elements distant from target genes.
- These long-range elements interact physically with gene promoters, influencing expression.
- Current methods lack the resolution to link these elements to specific genes genome-wide.
Purpose of the Study:
- To develop a high-resolution genome-wide method for linking regulatory elements to their target promoters.
- To create the first comprehensive catalog of long-range interacting elements and their associated genes.
- To investigate the functional and regulatory characteristics of these distal elements.
Main Methods:
- Utilized a sequence capture approach to enrich Hi-C libraries for over 22,000 mouse promoters.
- Identified statistically significant long-range interactions at restriction fragment resolution.
- Analyzed interactions in mouse embryonic stem cells and fetal liver cells.
Main Results:
- Successfully assigned long-range interacting elements to their target genes genome-wide.
- Distal sites contacting active genes showed active histone modifications and transcription factor binding.
- Inactive genes contacted distal sites with repressive histone marks.
- Coregulated genes, particularly developmental transcription factors in ES cells, clustered nonrandomly in spatial networks.
Conclusions:
- Established the first genome-wide catalog linking gene promoters to long-range interacting regulatory elements.
- Demonstrated the regulatory potential of distal elements based on associated epigenetic marks.
- Highlighted complex spatial regulatory circuitry and functional gene clustering in mammalian gene expression.
