A comparative analysis of transcribed genes in the mouse hypothalamus and neocortex reveals chromosomal clustering

Abstract

The hypothalamus and neocortex are subdivisions of the mammalian forebrain, and yet, they have vastly different evolutionary histories, cytoarchitecture, and biological functions. In an attempt to define these attributes in terms of their genetic activity, we have compared their genetic repertoires by using the Serial Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus tags with 125,296 neocortical tags, we demonstrate that each structure possesses a different transcriptional profile in terms of gene ontological characteristics and expression levels. Despite its more recent evolutionary history, the neocortex has a more complex pattern of gene activity. Gene identities and levels of gene expression were mapped to their chromosomal positions by using in silico definition of GC-rich and GC-poor genome bands. This analysis shows contrasting views of gene activity on a genome scale that is unique to each brain substructure. We show that genes that are more highly expressed in one tissue tend to be clustered together on a chromosomal scale, further defining the genetic identity of either the hypothalamus or neocortex. We propose that physical proximity of coregulated genes may facilitate transcriptional access to the genetic substrates of evolutionary selection that ultimately shape the functional subdivisions of the mammalian brain.

Molecular networks involved in mouse cerebral corticogenesis and spatio-temporal regulation of Sox4 and Sox11 novel antisense transcripts revealed by transcriptome profiling

“…The number of unique tags in each library ranges from approximately 7,200 to 32,000 due to the variation in library size (approximately 13,500 to 70,000). The distribution of tag abundance, however, is similar in all libraries (Figures S1 and S2 in Additional data file 1), in which the majority of tags were detected only once (58 to 76% or approximately 5,500 to approximately 24,000 tags), representing a trend comparable with previously reported SAGE analyses of mouse neocortices [27,29]. Of all unique tags, only 5,199 (approximately 2.4%) are common to all developmental stages.…”

Structure and function of the human genome

“…However, Yamashita et al (2004) identified large-scale functional clustering of genes that were coexpressed in specific human tissues. Boon et al (2004) and Petkov et al (2005) reported similar results in the mouse, and Caron et al (2001) reported clustering of genes expressed at high levels into specific chromosomal regions. Importantly, the clusters do not appear to be the products of evolutionary duplications of an ancestral gene(s), and the implication is that clustering reflects some level of coordinate control, speculatively, such as enhancer sharing or open chromatin conformation.…”

A Serial Analysis of Gene Expression Profile of the Alzheimer’s Disease Tg2576 Mouse Model

“…The Tg2576 and NTg libraries were produced using the I-SAGE kit (Invitrogen, Mt. Waverley, Australia) following the manufacturer's SAGE 1.0d protocol, which has been previously described in the literature (Margulies et al 2001;Boon et al 2004). Equal amounts of RNA extracted from each mouse were pooled for use in each of their respective libraries, with a total of 5 lg of pooled RNA used.…”