Although it is possible to create more gene sets in silico (e.g. through chromosome neighborhoods, expression neighborhoods and regulatory motif sharing, etc)., the increasing functional heterogeneity associated with such less-curated gene sets make them difficult for subsequent interpretation in terms of biological mechanism.
In order to test our hypothesis that deacetylation sites function as a boundary complex and partition the neighborhood gene expression domains, we correlated histone deacetylated sites with gene expression profiles as follows.
By clustering proteins into distinct groups based on their neighborhood gene expression characteristics, we identify several significant trends in the dynamic organization of the protein interaction network.
We show that proteins with distinct neighborhood gene expression characteristics are positioned in specific localities in the protein interaction network thereby playing specific roles in the dynamic network connectivity.
In this model, co-regulation within an expression neighborhood is due to incidental interactions between transcriptional enhancers and promoters [ 16].
In addition, supporting the functional diversity revealed by our gene neighborhood analysis, the expression of the eight other COG0523 family members from C. reinhardtii are not significantly affected by the deficiency of metals tested.
We then studied several spatial hybridization patterns and showed that, in many cases, a selective brain atlas can represent an expression neighborhood that consists of genes of statistically enriched function categories.
These co-expressed genes create clusters of expression neighborhoods [ 13] which are conserved by natural selection [ 14] A study in Arabidopsis showed clusters of up to 20 different genes were coordinately regulated, with a median cluster size of 100 kb [ 15].
Our results suggest that different regulatory mechanisms may apply to each of the three promoter classes, and provide a mechanism for "gene expression neighborhoods," local clusters of co-expressed genes.
To illustrate the difference between disrupted expression neighborhoods of significant candidate genes and not significant genes, we have added graphs containing the queried neighborhood of the candidates (Figures S1, S2, S3).
