Genome complexity: DNA in 3D follows patterns (Introduction)

by David Turell @, Friday, December 11, 2015, 18:54 (1379 days ago) @ David Turell

DNA is grouped around genes to facilitate expression:

"[W]e need to think about the structure of the genome in 3D space because that is how we now understand that genes are regulated," says Xiong Ji, a postdoctoral researcher in the Young lab and a co-author of the Cell Stem Cell paper.

"One of Ji's co-authors, graduate student Daniel Dadon, agrees. "This three-dimensional information helps us to interpret regulatory and mutational data with unprecedented accuracy. It's not just a bag of genes and regulatory elements in the nucleus -- this is a highly organized structure that confers function."

"Previous research in mouse ES cells by Young's lab and others determined that a chromosome's DNA is formed into loops that are anchored at their bases by proteins called CTCFs. The benefits of the loops are two-fold. First, the loops help organize and package two meters of DNA to fit into a nucleus that is approximately 5 micrometers in diameter. Second, each loop creates an insulated neighborhood that restricts the action of a regulatory element to genes that resides in the same loop. As graduate student and co-author Diego Borges-Rivera states, "The genome's 3D shape is a key mechanism underlying gene regulation."

"By studying human ES cells, scientists in the Young lab and the lab of Whitehead Founding Member Rudolf Jaenisch created an initial genome map consisting of 13,000 loops established by CTCF anchors and determined that the average insulated neighborhood is 200 kb in length and contains a single gene. The team found that most of the the mapped CTCF anchor sites in the human ES cells genome are maintained in other human cell types and furthermore, that these loop anchor sequences are highly conserved in primate genomes. Such a surprising degree of conservation indicates that these neighborhoods create a foundational framework for gene regulation that is maintained throughout development and across species."

Comment: Mentioned many times before, the 3-D relationships are carefully laid out, as if designed, and put to shame the argument from 'junk DNA'.

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