Coordinate gene regulation during hematopoiesis is related to genomic organization.
Gene loci are found in nuclear subcompartments that are related to their expression status. For instance, silent genes are often localized to heterochromatin and the nuclear periphery, whereas active genes tend to be found in the nuclear center. Evidence also suggests that chromosomes may be specifically positioned within the nucleus; however, the nature of this organization and how it is achieved are not yet fully understood. To examine whether gene regulation is related to a discernible pattern of genomic organization, we analyzed the linear arrangement of co-regulated genes along chromosomes and determined the organization of chromosomes during the differentiation of a hematopoietic progenitor to erythroid and neutrophil cell types. Our analysis reveals that there is a significant tendency for co-regulated genes to be proximal, which is related to the association of homologous chromosomes and the spatial juxtaposition of lineage-specific gene domains. We suggest that proximity in the form of chromosomal gene distribution and homolog association may be the basis for organizing the genome for coordinate gene regulation during cellular differentiation.
Kosak
Steven T
ST
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. skosak@fhcrc.org
Scalzo
David
D
Alworth
Sam V
SV
Li
Fusheng
F
Palmer
Stephanie
S
Enver
Tariq
T
Lee
James S J
JS
Groudine
Mark
M
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D045584:Chromosome Positioning / Q000235:genetics*; D041905:Erythroid Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis