Interesting article...

[Guest guest]

Hmm, I wonder if this might be of consequence in looking for ways to treat SMA

and other genetic diseases? I just found it interesting. What do y'all think?

Blessings,

Holly

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Printer Friendly Format from NY Times today.

July 25, 2006

Scientists Say They’ve Found a Code Beyond Genetics in DNA

By NICHOLAS WADE

Researchers believe they have found a second code in DNA in addition to the

genetic code.

The genetic code specifies all the proteins that a cell makes. The second code,

superimposed on the first, sets the placement of the nucleosomes, miniature

protein spools around which the DNA is looped. The spools both protect and

control access to the DNA itself.

The discovery, if confirmed, could open new insights into the higher order

control of the genes, like the critical but still mysterious process by which

each type of human cell is allowed to activate the genes it needs but cannot

access the genes used by other types of cell.

The new code is described in the current issue of Nature by Eran Segal of the

Weizmann Institute in Israel and Widom of Northwestern University in

Illinois and their colleagues.

There are about 30 million nucleosomes in each human cell. So many are needed

because the DNA strand wraps around each one only 1.65 times, in a twist

containing 147 of its units, and the DNA molecule in a single chromosome can be

up to 225 million units in length.

Biologists have suspected for years that some positions on the DNA, notably

those where it bends most easily, might be more favorable for nucleosomes than

others, but no overall pattern was apparent. Drs. Segal and Widom analyzed the

sequence at some 200 sites in the yeast genome where nucleosomes are known to

bind, and discovered that there is indeed a hidden pattern.

Knowing the pattern, they were able to predict the placement of about 50 percent

of the nucleosomes in other organisms.

The pattern is a combination of sequences that makes it easier for the DNA to

bend itself and wrap tightly around a nucleosome. But the pattern requires only

some of the sequences to be present in each nucleosome binding site, so it is

not obvious. The looseness of its requirements is presumably the reason it does

not conflict with the genetic code, which also has a little bit of redundancy or

wiggle room built into it.

Having the sequence of units in DNA determine the placement of nucleosomes would

explain a puzzling feature of transcription factors, the proteins that activate

genes. The transcription factors recognize short sequences of DNA, about six to

eight units in length, which lie just in front of the gene to be transcribed.

But these short sequences occur so often in the DNA that the transcription

factors, it seemed, must often bind to the wrong ones. Dr. Segal, a

computational biologist, believes that the wrong sites are in fact inaccessible

because they lie in the part of the DNA wrapped around a nucleosome. The

transcription factors can only see sites in the naked DNA that lies between two

nucleosomes.

The nucleosomes frequently move around, letting the DNA float free when a gene

has to be transcribed. Given this constant flux, Dr. Segal said he was surprised

they could predict as many as half of the preferred nucleosome positions. But

having broken the code, “We think that for the first time we have a real

quantitative handle” on exploring how the nucleosomes and other proteins

interact to control the DNA, he said.

The other 50 percent of the positions may be determined by competition between

the nucleosomes and other proteins, Dr. Segal suggested.

Several experts said the new result was plausible because it generalized the

longstanding idea that DNA is more bendable at certain sequences, which should

therefore favor nucleosome positioning.

“I think it’s really interesting,” said Bradley Bernstein, a biologist at

Massachusetts General Hospital.

Jerry Workman of the Stowers Institute in Kansas City said the detection of the

nucleosome code was “a profound insight if true,” because it would explain many

aspects of how the DNA is controlled.

The nucleosome is made up of proteins known as histones, which are among the

most highly conserved in evolution, meaning that they change very little from

one species to another. A histone of peas and cows differs in just 2 of its 102

amino acid units. The conservation is usually attributed to the precise fit

required between the histones and the DNA wound around them. But another reason,

Dr. Segal suggested, could be that any change would interfere with the

nucleosomes’ ability to find their assigned positions on the DNA.

In the genetic code, sets of three DNA units specify various kinds of amino

acid, the units of proteins. A curious feature of the code is that it is

redundant, meaning that a given amino acid can be defined by any of several

different triplets. Biologists have long speculated that the redundancy may have

been designed so as to coexist with some other kind of code, and this, Dr. Segal

said, could be the nucleosome code.

Copyright 2006 The New York Times Company