Study uncovers how DNA unfolds for transcription

January 17, 2012 By Krishna Ramanujan
Live cell microscope images show histones (green) at heat shock genes (indicated by the dotted lines), which are highly condensed under normal conditions (top). When the temperature of cells is raised, heat shock genes undergo extensive disruption (below) as seen by the formation of large puffs with RNA Polymerase II (red), as the histones unpack to make the gene available for expression. Image: Martin Buckley

( -- The human genome contains some 3 billion base pairs that are tightly compacted into the nucleus of each cell. If a DNA strand were the thickness of a human hair, the entire human genome would be crammed into a space the size of a softball, but if it were unraveled and all the strands lined up, they would stretch from Ithaca, N.Y., to Boston.

A Cornell study, published in the Jan. 13 issue of Molecular Cell, teases out how cells undergo transcription, where compacted DNA unravels, and a complex enzyme called reads the desired gene's and transcribes them into RNA. The RNA then instructs the cell to make specific proteins based on a gene's blueprint.

In particular, the researchers expand on their previous work that showed that the unraveling of compacted DNA occurs independently of transcription by RNA polymerase II. Many scientists previously believed that RNA polymerase II played a major role in decompacting the DNA.

"The process by which nucleosomes [coiled packets of DNA] become decompacted -- especially during transcription -- hadn't been well characterized until the last decade," said Steven Petesch, the paper's lead author and a graduate student in the lab of John Lis, the paper's senior author and the Barbara McClintock Professor of and Genetics at Cornell. "If you want to understand how basic processes like transcription occur, then you need to understand the steps that facilitate that process," Petesch added.

To tease out such processes, Petesch and Lis used from , which become activated when temperatures rise above a threshold, such as during hot days for fruit flies or when people get fevers. The genes, which are found in many organisms, initiate processes that protect cells from damage. By applying heat, the researchers were able to jump-start within seconds the unfolding of DNA and the transcription of heat shock genes.

When the temperature rises, a protein called a heat shock factor facilitates the steps necessary for transcription to occur. Among other things, Petesch and Lis found that heat shock factor binds to the heat shock genes and activates processes involving key enzymes that ultimately cause the enzyme Poly(ADP-ribose) polymerase (PARP) to locally produce Poly(ADP-Ribose) (PAR), a long polymer similar to DNA and RNA.

When DNA is compacted, strands wrap tightly around proteins called histones, like thread wrapped around a spool, to create packets of nucleosomes. But, it turns out, PAR competes with DNA for binding of histone proteins, which helps them unwrap from their spools and decompact. The researchers found that within seconds of increasing temperatures, heat shock factor is recruited to start the process of modifying histones and the unfolding of the DNA before transcription occurs.

"This process is completely independent of RNA Polymerase II transcribing through the gene," said Petesch. Lis added, "However, this process is completely dependent on heat shock factor and PARP's ability to make PAR chains, which are necessary to rapidly remove nucleosomes and unravel the induced gene."

PARP has been known for decades as important for DNA repair and is targeted in some cancer treatments.

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1 / 5 (6) Jan 17, 2012
So what they're saying is that there's more than one way to unravel the DNA, in this case it appears to be some kind of emergency response to uncontrolled increase in heat.

Now, of course one needs to ask the question: Since this is a basic procedure of a living cell, and it is now already superimposed on the normal unraveling, just how did life get to kick-start all by random physical process with such complex processes already required? Surely the cell would not have been able to survive the heat without it. Evolution could not even have started. Where and how did this complex thing called life arise all by itself, without the help of a super-intelligent outside agent? Maybe it's not the creationists who believe in fairy tales.
5 / 5 (4) Jan 17, 2012
Surely the cell would not have been able to survive the heat without it.

Those that didn't were weeded out. It's called natural selection. say it with me : Na-tuh-rahl-say-lec-shun

It's the same principle that will see to it that you will not breed.
5 / 5 (2) Jan 17, 2012
@kev - those complexities are not required for simple life.
However even slight tendencies to undo the effects of heat were advantageous because they slightly increased an organism's chances of having extra offspring.
As surviving creatures exchanged genes (yes, even single-celled creatures exchange genes), creatures with more such slight changes did even better.
Even a 1% advantage accumulates quickly over geological time scales (the earth really is older than 6000 years).
Try multiplying 1.01 by itself. Huh - just 1.02, not much change. Now try it 70 times. Huh - that about 2. Now try 700 times. Wow - that's 1000.
Bacteria often divide several times per day, so 700 times is on the order of a year. In 3 years an advantage can spread itself a billion times (10^9), and that gives it a billion chances to meet another advantage. Now try an ocean full of creatures and thousands and millions and billions of years.
1 / 5 (1) Jan 18, 2012
It is quite obvious that you are very poorly educated in the field of micro-biology, physics, and chemistry. If your hypothesis were true, you would not be capable of reading this thread, as the following pre-existing conditions must be met before any sort of organized conditions can be realized: a) Intelligence (or self-aware entity possessing pre-existing knowledge of otherwise un-knowable circumstances), b) information, and c) infinite energy potential.
Now, please define for me, if you can, the several thousand step process by which photons are meaningfully converted into useful visual information. Mathematically, the entire process is so complex as to be rendered impossible by chance. It can be easily calculated.
Now, if one step doesn't work we just 'weed it out'? ? No, the system must first have prior knowledge of the behaviour of light particles/waves, the effect of camera obscura, etc, etc, etc, and on and on it goes to infinity.
1 / 5 (1) Jan 23, 2012
Glade space/time had prior "knowledge" to a force labeled gravitational force. Any particle label as a particle is
lost without that.

Energy has infinite form. So how many forms are we able to access? Presently, anyone faced with the infinite - the concept - will sort this out arbitrarily via randomness.

Or let God sort/weed this out - let God sort/weed this out for you ad infinitum.

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