Pernilla Bjerling

Department of Medical Biochemistry and Microbiology, Uppsala University. Home page

Research: Spatial organisation of genes in the nucleus

The complete genomic map of humans is known. Now we have the task to determine the function of all the genes. We also need to understand the regulation of the genes. There are a growing number of examples where sub-nuclear location influences the gene activity. For example, in fission yeast, Schizosaccharomyces pombe, a simple eukaryotic model system, it has been shown that the centromeres and telomeres are localised to the nuclear periphery. Furthermore, when genes are inserted into these areas of the chromosomes they are transcriptionally repressed. The location of a certain part of the chromosome can now be studied live using real-time fluorescence microscopy due to the help of Green Fluorescent Protein (GFP). GFP is fused to the E. coil Lac Repressor protein (Lac-R) and expressed ectopically in the cell where tandem repeats of the lacO sequence has been inserted into the area of interest of the chromosome. Gene loci will be labelled by insertion via homologous recombination of tandem repeats of the lacO sequence. Homologous recombination occurs frequently in S. pombe and is a highly efficient way to introduce markers at specific loci. We are currently investigating the localisation of the mating-type region. The mating-type region consists of an expressed locus, mat1, that determines the mating-type P or M. Homothallic strains switches mating-type by utilising two transcriptionally repressed cassettes mat2-P and mat3-M where the mating-type information is stored. We will compare the localisation of the mating-type region in a wild-type strain to the localisation in a mutated strain where mat2-P and mat3-M is expressed. In addition, we are interested in finding out what proteins targets the telomeres to the nuclear periphery. We are planning to do a mutant screen using a strain with a lacO labelled telomere and a reporter gene. We will screen for elevated expression of the reporter gene and thereafter for mislocalisation of the telomere.

Five Selected Publications

A novel type of silencing factor, Clr2, is necessary for transcriptional silencing at various chromosomal locations in the fission yeast Schizosaccharomyces pombe. Bjerling P., Ekwall K., Egel R., and Thon G. NAR (2004) 32: 4421-442

Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity. Nakayama J., Xiao G., Noma K., Malikzay A., Bjerling P., Ekwall K., Kobayashi R., Grewal SI. EMBO J. (2003) 22: 2776-2787

Functional divergence of histone deacetylases by distinct localisation and specificity in fission yeast. Bjerling, P., Silverstein, R., Thon, G., Caudy A., Grewal, S. and Ekwall, K. MCB (2002) 22: 2170-2181

Expression state boundaries in the mating-type region of fission yeast. Thon G., Bjerling P., Bunner C. and Verhein-Hansen J. Genetics (2002) 161: 611-622

Hrp3, a chromodomain helicase/ATPase DNA binding protein, is required for heterochromatin silencing in fission yeast. Yoo, E.J., Jang, Y.K., Lee, M.A., Bjerling, P., Kim, J.B., Ekwall, K., Seong, R.H. and Park, S.D. BBRC (2002) 295: 970-974