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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
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Three-dimensional genome architecture and emerging technologies: looping in disease
Arpit Mishra1, R David Hawkins2
1Division of Medical Genetics, Department of Medicine, Department of Genome Sciences, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, 98195-5065, USA.
Genome Medicine
|October 2, 2017
Summary
Genome compaction, regulated by proteins and RNAs, shapes 3D genome architecture. Advances in 3D genomics enhance understanding of disease mechanisms and offer therapeutic potential.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Cellular genome compaction is a key regulator of gene expression.
- Architectural proteins, long non-coding RNAs (lncRNAs), and regulatory DNA maintain genome structure.
- This 3D genome organization involves complex regulatory circuits controlling gene expression.
Purpose of the Study:
- To review the current state of 3D genome organization.
- To focus on how technological advances in 3D genomics improve understanding of disease mechanisms.
- To explore the therapeutic potential of manipulating 3D genome architecture.
Main Methods:
- Utilizing genome-wide chromatin conformation capture (Hi-C) and capture Hi-C technology.
- Mapping interactions between gene promoters and distal regulatory elements like enhancers.
- Leveraging genome-wide association studies (GWASs) to identify disease-associated variants in regulatory elements.
Main Results:
- Recent technological advances provide enhanced insights into 3D genome organization.
- Disease variants are frequently enriched in regulatory elements like enhancers.
- Aberrations in architectural units correlate with various pathological outcomes.
Conclusions:
- 3D genome architecture is crucial for gene regulation and cellular function.
- Advanced 3D genomics techniques are vital for dissecting disease mechanisms.
- Engineering 3D genome structure presents novel therapeutic avenues for genetic disorders.
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