Unveiling the Human Genome's 3D Structure: Breakthroughs in Understanding Gene Expression and Cellular Function

Researchers from Weill Cornell Medicine and the New York Genome Center, in collaboration with Oxford Nanopore Technologies, have made a groundbreaking discovery in understanding the three-dimensional structure of the human genome. By developing a novel method using genome-scale nanopore sequencing, they have demonstrated that cell function, including gene expression, is influenced by groups of simultaneously interacting regulatory elements in the genome. This finding challenges the traditional understanding that gene expression is governed by pairs of regulatory elements.

Key Takeaways:

• The researchers used genome-scale nanopore sequencing to assess the three-dimensional structure of the human genome, revealing that groups of regulatory elements interact simultaneously to affect cell function and gene expression.
• The new technology, Pore-C, combines chromatin conformation capture with nanopore sequencing of concatemers to profile proximal high-order chromatin contacts at the genome scale.
• A statistical method, Chromunity, was developed to identify sets of genomic loci with frequencies of high-order contacts significantly higher than background ("synergies").
• Synergies were enriched in enhancers and promoters in active chromatin and in highly transcribed and lineage-defining genes in human cell lines.
• In prostate cancer cells, synergies included binding sites of androgen-driven transcription factors and the promoters of androgen-regulated genes.
• Concatemers of high-order contacts in highly expressed genes were demethylated relative to pairwise contacts at the same loci.
• Synergies in breast cancer cells were associated with tyfonas, a class of complex DNA amplicons.

Statistics:

• 1 million readers per month for Brian Wang's blog, Nextbigfuture.com (Source: [1])
• Ranked #1 Science News Blog (Source: [1])
• High-order 3D chromatin interactions between more than two genomic loci are commonly found in human chromatin (Source: [1])
• Previous high-order 3D chromatin assays measured distant interactions across the genome or proximal interactions at selected targets (Source: [1])
• Genome-scale nanopore sequencing was used to assess the three-dimensional structure of the human genome (Source: [1])

Sources:

• [1] Nature Biotechnology -- high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing
• [2] Weill Cornell Medicine (mentioned in the article, but no source explicitly cited)
• [3] Oxford Nanopore Technologies (mentioned in the article, but no source explicitly cited)
• [4] Brian Wang's blog, Nextbigfuture.com