Where the expressed genes are
Study of chromatin distribution overturns theory that accessibility governs
expression | By Cathy Holding

Despite widely held beliefs that open and condensed regions of chromatin
correlate with active and silent regions of expression, respectively, there
is no strict correlation between open chromatin and the activity of a gene,
according to a paper in Cell this week. Instead, genes that need to be
rapidly activated or switched off are held in regions of open chromatin
structure-possibly constraining certain genes to lie within the same genomic
region throughout evolution, according to lead author Wendy A. Bickmore of
the MRC Human Genetics Unit in Edinburgh.

"Previously, chromatin structures have really only been studied as
individual genes, one by one, so we wanted to take a more global approach to
ask questions about how chromatin is organized across the whole human
genome," Bickmore told The Scientist.

Bickmore's team labelled the DNA from open or closed chromatin by
fluorescence in situ hybridization (FISH) so they appeared either green or
red, respectively, and hybridized them to metaphase chromosomes. At a
subchromosome level, gene-rich T-bands-for example at the distal end of 1p
(1p34-p36), and at 11q13 and q23-were enriched in open chromatin. Their
microarray analysis confirmed the gross picture derived from the FISH data.

"We already knew that human genes are not uniformly spread across the whole
genome, they tend to be clustered together in fairly tight clusters, and
these are the genes that corresponded with the open chromatin," Bickmore
said.

The study marries biochemistry with morphology, according to Tom Misteli who
heads the Cell Biology of Gene Expression Group at the US National Cancer
Institute. "A biochemical definition of chromatin is taken and then applied
to chromosomes and to the linear sequence of the genome," said Misteli, who
was not involved in the study. The result is a fairly low-resolution map of
the chromatin fiber. "So this is the next level from the genome
sequence-that's the significance. It's the first study to map the chromatin
fiber genome-wide," said Misteli.

Full text at TheScientist
http://www.biomedcentral.com/news/20040906/02

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