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Steven T Kosak

Publications and source records attributed to Steven T Kosak.

5 recordsLinked to original sources
PubMed2004

Gene order and dynamic domains.

When considering the daunting complexity of eukaryotic genomes, some comfort can be found in the fact that the human genome may contain only 30,000 to 40,000 genes. Moreover, growing evidence suggests that genomes may be organized in such a way as to take advantage of space. A gene's location in the linear DNA sequence and its position in the three-dimensional nucleus can both be important in its regulation. Contrary to prevailing notions in this postgenomic era, the bacteriophage lambda, a paragon of simplicity, may still have a few things to teach us with respect to these facets of nonrandom genomes.

Animals↗
PubMed2004

Form follows function: The genomic organization of cellular differentiation.

The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.

Animals↗
PubMed2003

A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements.

Recent studies of nuclear organization have shown an apparent correlation between the localization of genes within the interphase nucleus and their transcriptional status. In several instances, actively transcribed gene loci have been found significantly looped away from their respective chromosome territories (CTs), presumably as a result of their expression. Here, we show evidence that extrusion of a gene locus from a CT by itself is not necessarily indicative of transcriptional activity, but also can reflect a poised state for activation. We found the murine and a wild-type human beta-globin locus looped away from their CTs at a high frequency only in a proerythroblast cell background, prior to the activation of globin transcription. Conversely, a mutant allele lacking the locus control region (LCR), which is required for high-level globin expression, was mostly coincident with the CT. The LCR may thus be responsible for the localization of the globin locus prior to activation. Replacement of the LCR with a B-cell-specific regulatory element, while also extruding the globin locus, brought it closer to the repressive centromeric heterochromatin compartment. We therefore suggest that the looping of gene loci from their CTs may reflect poised and repressed states, as well as the previously documented transcriptionally active state.

Animals↗
PubMed2002

Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.

Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igkappa loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally configured in pro-B nuclei. The inactive loci at the periphery do not associate with centromeric heterochromatin. Upon localization away from the nuclear periphery in pro-B cells, the IgH locus appears to undergo large-scale compaction. We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development.

Animals↗