Gene expression neighborhoods

Abstract
Reductionist approaches have been a tremendous boon to understanding the
regulation of transcription, but new findings suggest that genes may also be subject
to regulation according to their location within the genome.
It has been clear for some time that genomic location has some impact on gene
expression, and that even subtle differences in gene expression can have
consequences in some circumstances.
Spellman and Rubin found that neighborhoods composed of 15 contiguous genes
had similar relative expression levels, although the neighborhoods were not
obviously composed of genes with related functions.
Two recent papers suggest that genes with similar expression levels are non-
randomly distributed, in this case within the human genome. In Drosophila, however,
this is less likely, because embryos and adults show two different housekeeping
gene sets.
Perhaps the simplest explanation for co-regulation within an expression
neighborhood is that strong transcriptional activators, such as the yeast protein
GAL4, create new neighborhoods. However, the data presented by Spellman and
Rubin suggest that the pattern of gene expression within a neighborhood is
essentially a 'square wave'.
Spellman and Rubin [3] favor a structural chromatin domain model, which involves
opening of the chromatin of an entire neighborhood as a result of activation of a
target gene within the neighborhood. This model is inconsistent with neighborhoods
of co-regulation, but could explain why some genes are up-regulated and some
down-regulated.
Spellman and Rubin tested a short list of known chromosomal structures to look for
correlations with expression neighborhoods, but found none. It is increasingly clear
that the nucleus is a highly organized three-dimensional space, and the hunt for the
structural basis of expression neighborhoods will be an exciting one.
Spellman and Rubin suggest that expression neighborhoods mean nothing, and that
inappropriate expression of gene neighbors does no harm, but deletions removing
greater than 1% of the Drosophila genome have severe dominant deleterious effects
on the organism.
Expression neighborhoods are likely to be functionally significant because they favor
the evolution of genes that benefit by being within that neighborhood. If expression
neighborhoods are maintained intact through evolutionary time, they may provide
evolution with additional tools with which to work.