3D Maps Find Loops in Human Genome
Tuesday 21 November, 2017
Peer Reviewed

3D Maps Find Loops in Human Genome

Published On: Tue, Dec 16th, 2014 | Molecular Biology | By BioNews

Researchers, including one of Indian origin, have assembled the first high-resolution, 3D maps of entire folded genomes, showing how a ‘genomic origami’ or folding allows the same genes to produce different cells.

The five-year project to identify the loops in the human genome was a collaboration between researchers at Harvard University, Baylor College of Medicine, Rice University and the Broad Institute of Harvard and MIT.

Loops form when two bits of DNA that are far apart in the genome sequence end up in close contact in the folded version of the genome in a cell’s nucleus.

From left, Erez Lieberman Aiden, Harvard graduate student Miriam Huntley and Suhas Rao of Baylor College of Medicine's Center for Genome Architecture. Credit: A. Sanchez/Baylor College of Medicine

From left, Erez Lieberman Aiden, Harvard graduate student Miriam Huntley and Suhas Rao of Baylor College of Medicine’s Center for Genome Architecture. Credit: A. Sanchez/Baylor College of Medicine

Researchers used a technology called “in situ Hi-C” to collect billions of snippets of DNA that were later analysed for signs of loops. The team found that loops and other genome folding patterns are an essential part of genetic regulation.

“More and more, we’re realising that folding is regulation,” said study co-first author Suhas Rao, a researcher at Baylor’s Centre for Genome Architecture.

“When you see genes turn on or off, what lies behind that is a change in folding. It’s a different way of thinking about how cells work,” said Rao.

“Our maps of looping have revealed thousands of hidden switches that scientists didn’t know about before. In the case of genes that can cause cancer or other diseases, knowing where these switches are is vital,” co-first author Miriam Huntley, a doctoral student at Harvard’s School of Engineering and Applied Sciences, said.

“The new maps allow us to really see, for the first time, what folding looks like at the level of individual genes,” said senior author Erez Lieberman Aiden, assistant professor of genetics at Baylor.

The research appears in the journal Cell.

Reference:

Rao, Suhas S.P. et al. A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping. Cell, 2014

Scientific Summary:

We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ?10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.

Leave a comment

XHTML: You can use these html tags: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

More from Molecular Biology
  • Scientists discover mechanisms necessary for the formation of heterochromatin