The field of epigenetics may have been literally scratching the surface

Genes are not drivers - cellular mechanisms control which stretches of DNA are accessible to be read out and translated into proteins

Excerpt: "Epigenetics—the study of genome modifications that control cell fate, some of which are thought to reflect environmental influences on the genetics of health and disease—is one of the key frontiers of modern genomics. At the heart of epigenetics is the question of how cells control which stretches of DNA are accessible to be read out and translated into proteins, and which sequences are spooled away and archived on nucleosomes.

The dominant model in the field portrays nucleosomes as passive spindles, themselves 'octamers' made up of eight blocks of rigid histone proteins that snap together like Lego pieces when wrapped in DNA, and which must break apart or slide out of the way to allow their archived DNA to become active again. But Sinha, Gross and Narlikar's new study promises to change this paradigm, demonstrating that nucleosomes are capable of shifting like putty in response to as-yet unknown signals.

"The field of epigenetics may have been literally scratching the surface," Narlikar said, referring to the field's focus on the function of epigenetic "marks," such as the chemical tags called methyl groups, on the exposed surfaces of histone proteins. "Altering the shape of the nucleosome, a fundamental building block of the chromosome, could in principle have large effects on processes ranging from genome organization to epigenetic inheritance."

In particular, according to Narlikar, a malleable nucleosome would make it possible for cells to read out segments of DNA without completely disassembling the nucleosome. This offers a potential explanation for mysterious histone modifications that would be buried uselessly deep inside the nucleosome according to the traditional model, and suggests a new mechanism for the extreme compaction chromosomes undergo during cell division, and offers potential answers to the chicken-and-egg problem of how cells know how to pull specific DNA sequences out of the archives without being first able to "see" them.

"If you look at crystal structures of the conventional model of the nucleosome, there's no slack, no room for the DNA to be pulled out. To read the DNA, you would have to move the whole histone octamer out of the way," Narlikar said. "What we're seeing is that you can keep them in place and still expose the DNA by changing the shape of the nucleosome."

The new discovery was made possible by a new and technically challenging nuclear magnetic resonance (NMR) method, which discerns features of chromatin dynamics that are invisible to other commonly used approaches. The technique revealed changes in how histones contact one another, demonstrating convincingly that nucleosomes are dynamic, rather than rigid.

In describing the work, Narlikar quoted Proust, who wrote, "The only true voyage of discovery, … would be not to visit strange lands but to possess other eyes, to behold the universe through the eyes of another…."

"The new NMR approach literally allowed us to look with 'other eyes,' and in doing so allowed us to discover a fundamental new property of chromatin," Narlikar said.

Much is still unknown, Narlikar said, about the details of nucleosomes' shape-shifting abilities, as well as what types of cellular biochemical signals regulate their dynamics, and exactly what effects these changes have on DNA regulation. "All of these ideas are speculative at this point. But we wouldn't have had the conceptual framework to think of any of these hypotheses until there was reason to think of the nucleosome as dynamic rather than rigid. The number of questions this opens up is incredibly exciting."

My comment: Genes are just raw material for clever cellular mechanisms that are regulated by several factors and influenced by diet, stress, climate and other environmental factors. Seeing this kind of complexity, 3D shape shifting and its affect to the regulation of how genes are used for protein production or hided from transcription machineries, points to Intelligent design and creation. There are only mechanisms that affect the protein production and randomness has no role within these clever processes. That's why the evolutionary theory and natural selection are the biggest lies ever.