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Scientists Say They=92ve = Found a Code=20 Beyond Genetics in DNA

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By NICHOLAS=20 WADE

Published: July 25, 2006

Researchers believe they have found a second code in DNA=20 in addition to the genetic code.

Skip=20 to next paragraph=20

=20

Loren Williams/Chemistry and Biochemistry, Georgia = Institute=20 of Technology

In a living cell, the DNA double helix wraps around a = nucleosome, above center, and binds to some of its proteins, known as = histones.=20

The genetic code specifies all the proteins that a cell makes. The = second=20 code, superimposed on the first, sets the placement of the nucleosomes,=20 miniature protein spools around which the DNA is looped. The spools both = protect=20 and control access to the DNA itself.

The discovery, if confirmed, could open new insights into the higher = order=20 control of the genes, like the critical but still mysterious process by = which=20 each type of human cell is allowed to activate the genes it needs but = cannot=20 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=20 Weizmann Institute in Israel and Jonathan Widom of Northwestern=20 University in Illinois and their colleagues.

There are about 30 million nucleosomes in each human cell. So many = are needed=20 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=20 up to 225 million units in length.

Biologists have suspected for years that some positions on the DNA, = notably=20 those where it bends most easily, might be more favorable for = nucleosomes than=20 others, but no overall pattern was apparent. Drs. Segal and Widom = analyzed the=20 sequence at some 200 sites in the yeast genome where nucleosomes are = known to=20 bind, and discovered that there is indeed a hidden pattern.

Knowing the pattern, they were able to predict the placement of about = 50=20 percent of the nucleosomes in other organisms.

The pattern is a combination of sequences that makes it easier for = the DNA to=20 bend itself and wrap tightly around a nucleosome. But the pattern = requires only=20 some of the sequences to be present in each nucleosome binding site, so = it is=20 not obvious. The looseness of its requirements is presumably the reason = it does=20 not conflict with the genetic code, which also has a little bit of = redundancy or=20 wiggle room built into it.

Having the sequence of units in DNA determine the placement of = nucleosomes=20 would explain a puzzling feature of transcription factors, the proteins = that=20 activate genes. The transcription factors recognize short sequences of = DNA,=20 about six to eight units in length, which lie just in front of the gene = to be=20 transcribed.

But these short sequences occur so often in the DNA that the = transcription=20 factors, it seemed, must often bind to the wrong ones. Dr. Segal, a=20 computational biologist, believes that the wrong sites are in fact = inaccessible=20 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=20 nucleosomes.

The nucleosomes frequently move around, letting the DNA float free = when a=20 gene has to be transcribed. Given this constant flux, Dr. Segal said he = was=20 surprised they could predict as many as half of the preferred nucleosome = positions. But having broken the code, =93We think that for the first = time we have=20 a real quantitative handle=94 on exploring how the nucleosomes and other = proteins=20 interact to control the DNA, he said.

The other 50 percent of the positions may be determined by = competition=20 between the nucleosomes and other proteins, Dr. Segal suggested.

Several experts said the new result was plausible because it = generalized the=20 longstanding idea that DNA is more bendable at certain sequences, which = should=20 therefore favor nucleosome positioning.

=93I think it=92s really interesting,=94 said Bradley Bernstein, a = biologist at Massachuse= tts=20 General Hospital.

Jerry Workman of the Stowers Institute in Kansas City said the = detection of=20 the nucleosome code was =93a profound insight if true,=94 because it = would explain=20 many aspects of how the DNA is controlled.

The nucleosome is made up of proteins known as histones, which are = among the=20 most highly conserved in evolution, meaning that they change very little = from=20 one species to another. A histone of peas and cows differs in just 2 of = its 102=20 amino acid units. The conservation is usually attributed to the precise = fit=20 required between the histones and the DNA wound around them. But another = reason,=20 Dr. Segal suggested, could be that any change would interfere with the=20 nucleosomes=92 ability to find their assigned positions on the DNA.

In the genetic code, sets of three DNA units specify various kinds of = amino=20 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=20 different triplets. Biologists have long speculated that the redundancy = may have=20 been designed so as to coexist with some other kind of code, and this, = Dr. Segal=20 said, could be the nucleosome code.

Nex= t Article=20 in Science (1 of 8) =BB

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Scientists=20 Hope to Unravel Neanderthal DNA (July 21, 2006)
The= Quest=20 for the $1,000 Human Genome (July 18, 2006)
BO= OKS; A=20 Peek Into the Remarkable Mind Behind the Genetic = Code (July=20 11, 2006)
Back to=20 Earth After Taking Fall From Genghis's Family = Tree (June 21,=20 2006)

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