Biological complexity: controlling DNA expression (Introduction)

by David Turell , Monday, October 23, 2017, 16:39 (2588 days ago) @ David Turell

Another giant enzyme is studied and its actions further understood:

https://phys.org/news/2017-10-single-molecule-developmental-gene.html

"Scientists at EPFL and Max Plank have made significant discoveries on how developmental genes are controlled by the methyltransferase enzyme PRC2.

"Polycomb repressive complex 2 (PRC2) is part of a larger system of proteins that work together to repress the expression of developmental genes. PRC2 does this by adding up to three methyl groups to a specific lysine amino acid (lysine 27) of the histone H3 protein. Trimethylation (three methyl groups) of lysine 27 in particular is important, as turns off the expression of specific genes during development.

"Such gene repression requires a high concentration of lysine 27 trimethylation within defined chromatin (DNA wrapped around histones) regions, since mutations that prevent this process result in developmental defects or cancer. For maximum activity, PRC2 needs further "accessory factors", which vary between species. In humans, a main accessory factor is PHF1.

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"Structural analysis showed that PHF1 contains a previously unknown DNA-binding domain whose interactions with the nucleosomal DNA is critical for anchoring PRC2 to chromatin and for increasing its activity. Essentially, this DNA-binding domain is the key to efficient gene regulation across different species. As the authors write: "...a major part of the binding affinity of PRC2 for nucleosomes comes from interactions of the complex with DNA."

"The authors draw three conclusions from the findings: First, that the binding affinity of PRC2 for chromatin substrate is determined by its interactions with DNA. Second, that increased anchoring of PRC2 to chromatin via PHF1 depends on a newly identified structural unit in PHF1. And third, that stable PRC2 chromatin interactions, mediated by PHF1, are key for increased lysine trimethylation in chromatin - and thus for gene repression."

Comment: Again extreme complexity in the controls of DNA expression. Cannot be accomplished by a chance process of evolution. Without strict control there would be developmental abnormalities. Obviously this whole system had to be developed all at once, intact, not bit by bit.