Genome complexity: DNA works in local regions (Introduction)

by David Turell , Tuesday, January 10, 2017, 14:00 (2656 days ago) @ David Turell

New research shows that DNA is organized into neighborhoods with gene modification controls and enhancers close by and limited to effect in aht regikon:

http://www.nytimes.com/2017/01/09/science/dna-tads.html?emc=edit_th_20170110&nl=tod...

"It turns out that the vast informational expanse of the genome is divvied up into a series of manageable, parochial and law-abiding neighborhoods with strict nucleic partitions between them — each one a TAD.

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"DNA is a super-long molecule packed into a very small space, and it’s clear that it’s not packed randomly,” Dr. Mundlos said. “It follows a very intricate and controlled packing mechanism, and TADs are a major part of the folding protocol.”

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"researchers soon realized there was much more to the genome than the protein codes it enfolded. “We were caught up in the idea of genetic information being linear and one-dimensional,” said Job Dekker, a biologist at the University of Massachusetts Medical School.

"For one thing, as the sequencing of the complete human genome revealed, the portions devoted to specifying the components of hemoglobin, collagen, pepsin and other proteins account for just a tiny fraction of the whole, maybe 3 percent of human DNA’s three billion chemical bases.

"And there was the restless physicality of the genome, the way it arranged itself during cell division into 23 spindly pairs of chromosomes that could be stained and studied under a microscope, and then somehow, when cell replication was through, merged back together into a baffling, ever-wriggling ball of chromatin — DNA wrapped in a protective packaging of histone proteins.

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"We realized that in order to understand how genetic information is controlled, we had to figure out how DNA was folded in space,” said Bing Ren of the University of California, San Diego.

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"Through chromosome conformation studies and related research, scientists have discovered the genome is organized into about 2,000 jurisdictions, and they are beginning to understand how these TADs operate.

"As with city neighborhoods, TADs come in a range of sizes, from tiny walkable zones a few dozen DNA subunits long to TADs that sprawl over tens of thousands of bases and you’re better off taking the subway. TAD borders serve as folding instructions for DNA. “They’re like the dotted lines on a paper model kit,” Dr. Dekker said.
TAD boundaries also dictate the rules of genetic engagement.

"Scientists have long known that protein codes are controlled by an assortment of genetic switches and enhancers — noncoding sequences designed to flick protein production on, pump it into high gear and muzzle it back down again. The new research indicates that switches and enhancers act only on those genes, those protein codes, stationed within their own precincts.

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“'Genes and regulatory elements are like people,” Dr. Dekker said. “They care about and communicate with those in their own domain, and they ignore everything else.”

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"Scientists are not entirely sure, but preliminary results indicate that the boundaries are DNA sequences that attract the attention of sticky, roughly circular proteins called cohesin and CTCF, which adhere thickly to the boundary sequences like insulating tape.

"Between those boundary points, those clusters of insulating proteins, the chromatin strand can loop up and over like the ribbon in a birthday bow, allowing genetic elements distributed along the ribbon to touch and interact with one another. But the insulating proteins constrain the movement of each chromatin ribbon, said Richard A. Young of the Whitehead Institute for Biomedical Research, and keep it from getting entangled with neighboring loops — and the genes and regulatory elements located thereon."

Comment: As I have commented in the past, only an understanding of DNA in 3-D will explain how it works to control gene expression. Only a brilliant mind can create a mechanism of code like DNA. God