Revolutionary new research has revealed how the human genome folds into an almost limitless variety of shapes so that individual cells can modulate their function.
The research, conducted by scientists from the Baylor College of Medicine, Rice University, the Broad Institute of MIT and Harvard, and Harvard University, also describes the first catalogue of DNA ’loops’ spanning the entire human genome.
Decoding the human genome began via the Human Genome Project in 1990. It was successfully decoded in April 2003 and essentially provides the complete genetic blueprint for building a human being.
“If DNA were a shoestring, you could make a loop anywhere. But within the cell, the formation of loops is highly constrained
Study co-author Suhas Rao
“For over a century, scientists have known that DNA forms loops inside of cells, and that knowing where the loops are is incredibly important,” said co-first author Suhas Rao, a researcher at the Centre for Genome Architecture at Baylor College.
“But mapping the positions of all those loops was long thought to be an insurmountable challenge.”
Previous research into DNA looping suggested that the human genome contains over one million loops.
However, Rao and his research team showed that the 3 billion DNA letters of the human genome are partitioned into roughly 10,000 loops - a surprisingly small number, Rao said.
According to the team’s research, DNA loops play a vital role in almost every process within a cell as many loops have genes at one end. When the loop forms, the gene ’turns on’, the researchers said.
“Folding drives function,” said co-first author Miriam Huntley.
“Our maps of looping revealed thousands of hidden switches that scientists didn’t know about before,” said Huntley.
“In the case of genes that can cause cancer or other diseases, knowing where these switches are is vital.”
The team’s research also revealed an interesting series of rules relating to how and where loops can form.
“If DNA were a shoestring, you could make a loop anywhere. But within the cell, the formation of loops is highly constrained,” said Rao.
“The loops we see almost all span fewer than 2 million genetic letters; they rarely overlap; and they are almost always associated with a single protein, called CTCF.”
According to researchers, CTCF is involved in the regulation of the 3D structure of chromatin, the building block of chromosomes.
“The most stunning discovery was about how CTCF proteins form a loop” said Eric Lander, a corresponding author on the paper.
“Even when they are far apart, the CTCF elements that form a loop must be pointing at each other - forming a genomic yin and yang.”
A full account of the study has been published in the journal Cell.