Genome complexity: 3-D DNA packing (Introduction)

by David Turell , Thursday, September 07, 2017, 05:35 (2636 days ago) @ David Turell

It is tightly packed in very short segments. Functional studies sow he following:

https://evolutionnews.org/2017/09/researchers-highlight-logistics-nightmare-facing-chro...

"What O’Shea’s team saw, in both resting and dividing cells, was chromatin whose “beads on a string” did not form any higher-order structure like the theorized 30 or 120 or 320 nanometers. Instead, it formed a semi-flexible chain, which they painstakingly measured as varying continuously along its length between just 5 and 24 nanometers, bending and flexing to achieve different levels of compaction. This suggests that it is chromatin’s packing density, and not some higher-order structure, that determines which areas of the genome are active and which are suppressed.

"We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus,” adds O’Shea. “It’s the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes.”

"An entry in the Oxford Science Blog asks, “How does a cell know which combination of the 20,000 genes it should activate to produce its specific toolkit?” Look in the formerly named junk DNA for clues:

"The answer to this question may be found in the pieces of DNA that lie between our protein-producing genes. Although our cells contain a lot of DNA, only a small part of this is actually composed of genes. We don’t really understand the function of most of this other sequence, but we do know that some of it has a function in regulating the activity of genes. An important class of such regulatory DNA sequences are the enhancers, which act as switches that can turn genes on in the cells where they are required.

"Switches are not junk. To show that they have important functional roles, the team looked at one enhancer called CTCF.

"Researchers have identified key proteins that appear to define and help organise this domain structure. One such protein is called CTCF, which sticks to a specific sequence of DNA that is frequently found at the boundaries of these domains. To explore the function of these CTCF boundaries in more detail and to investigate what role they may play in connecting enhancers to the right genes, our team studied the domain that contains the α-globin genes, which produce the haemoglobin that our red blood cells use to circulate oxygen in our bodies.

"Firstly, as expected from CTCF’s role in defining boundaries, we showed that CTCF boundaries help organise the α-globin genes into a specific domain structure within red blood cells. This allows the enhancers to physically interact with and switch on the α-globin genes in this specific cell type. We then used the gene editing technology of CRISPR/Cas9 to snip out the DNA sequences that normally bind CTCF, and found that the boundaries in these edited cells become blurred and the domain loses its specific shape. The α-globin enhancers now not only activate the α-globin genes, but cross the domain boundaries and switch on genes in the neighbouring domain.

“'Cells divide at least a billion times in the average person, usually without any problem.” Nevertheless, rare abnormalities do occur, as in the case with Down syndrome, when the wrong number of chromosomes (aneuploidy) results. ( my bold)

"Using high resolution microscopes to video the inner workings of live human cells, Dr Draviam and her colleagues at the University of Cambridge (UK) and the European Molecular Biology Laboratory in Heidelberg (Germany), discovered that two proteins — Aurora-B kinase and BubR1-bound PP2A phosphatase — act in opposition to each other, adding or removing phosphate groups respectively, to correctly control the attachment of microtubules to the chromosomes.

"Co-author Duccio Conti, who is Dr Draviam’s PhD student, said: “We found that a balance between Aurora-B kinase and BubR1-bound phosphatase is important to maintain correct chromosome numbers in human cells.'”

Comment: Packing DNA in a cell nucleus requires great complex compactification in order to give the right 3-D relationships for genes to be next to switches enhancers for proper expression of the genes. this is how 'Junk DNA' plays a major role, and obviously isn't junk. Obviously required design by God. Note my bold. The level of mistakes must be very small, but like a good designer, God recognized the need for backup corrective mechanisms to cover that possibility.