Kenneth Peterson

University of Kansas Cancer Center Cancer Biology – Associate Member
Biochemistry & Molecular Biology – Professor
Kidney Institute – Member
Department of Biochemistry and Molecular Biology

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Publications: Click here

Research Focus

Gene regulation, transcription, transcriptional control, developmental regulation, globin gene switching, fetal hemoglobin, gene activation & repression, high-throughput screen, hematopoiesis, erythropoiesis, animal models, transgenic mice, embryonic stem cells, gene regulation, chromatin, epigenetics, transcription, globin, LCR, hemoglobin, hematology, genetics, molecular biology, developmental biology, cell biology, repression, locus control region, transcriptional activators, transgenic mice, yeast artificial chromosomes

My major interest is genetic regulatory mechanisms with emphasis on the delineation of the function of locus control regions (LCRs). The human beta-globin locus serves as our primary model system. This locus consists of 5 functional genes arrayed in their order of expression during development, 5'-epsilon-Ggamma-Agamma-delta-beta-3'. The LCR is located 6- to 20-Kb upstream of the epsilon-globin gene. It is composed of five DNAseI-hypersensitive sites (HSs), which are highly conserved during evolution. The globin LCR has multiple properties, including the activation and maintenance of open chromatin domains, insulation from the effects of surrounding negative chromatin, conference of erythroid cell lineage specificity on globin gene expression and enhancement of globin gene transcription. LCRs or LCR-type elements have been identified in over 30 mammalian loci, but they are less understood compared to the beta-globin locus LCR. The mechanism of action of the LCR remains unknown.

Questions that I am pursuing include the structure/function relationships of the individual HSs composing the LCR, the structural features that are required for formation of the LCR holocomplex, the mechanism of interaction between the LCR and individual globin genes, and the mechanism whereby the LCR activates chromosomal domains. In my studies, I utilize yeast artificial chromosomes containing the entire beta-globin locus (beta-YACs). Mutations are introduced into the beta-YACs by homologous recombination in yeast without leaving exogenous DNA; the YACs are purified and microinjected into murine oocytes for the production of transgenic mice or transfected into established cell lines. Thus, the effect of these mutations on LCR function may be analyzed in the context of the intact beta-globin locus throughout development. I also study other genetic regulatory mechanisms and disease pathogenesis using transgenic mouse models of sickle cell disease, Alzheimer's disease, Kennedy's disease, polycystic kidney disease and Alport's syndrome.