Coordinate Gene Regulation During Hematopoiesis Is Related To Genomic Organization

Main Category: Genetics
Also Included In: Biology / Biochemistry
Article Date: 19 Nov 2007 - 17:00 PDT

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How are genomes, and the chromosomes that comprise them, organized in the eukaryotic nucleus? This long-standing question in cell biology has gained renewed interest due to observations that gene regulation is correlated with the nonrandom distribution of gene loci linearly along chromosomes and spatially within the nucleus. In a new study published this week in the open-access journal PLoS Biology, Steven Kosak and colleagues have used an in vitro model of cellular differentiation to test the hypothesis that there is an inherent organization of the genome related to coordinate gene regulation.

Their analysis reveals that during the differentiation of a murine hematopoietic (blood-forming cell) progenitor to derived cell types, co-regulated genes have a marked tendency to be proximal along chromosomes in the form of clusters (of two and three genes) and large-scale domains. Overall gene expression is also spatially proximal, with a pronounced concentration in the nuclear center.

The chromosomes themselves parallel this organization of gene activity, with chromosome territories localizing primarily in the interior of the nucleus. Surprisingly, the researchers found that homologous chromosomes have a tendency to be associated, the extent of which is related to the number of co-regulated genes residing on the particular chromosome. Furthermore, individual gene domains display lineage-specific proximity according to their co-regulation. This study supports the idea that the eukaryotic nucleus is broadly organized-with proximity playing a key role-to facilitate coordinated gene regulation during cellular differentiation.

Citation: Kosak ST, Scalzo D, Alworth SV, Li F, Palmer S, et al. (2007) Coordinate gene regulation during hematopoiesis is related to genomic organization. PLoS Biol 5(11): e309. doi:10.1371/journal.pbio.0050309.
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