Research: The Developmental Genetics Section is mainly interested in the genetics and molecular biology of gene silencing and mating-type switching in Schizosaccharomyces pombe. In this yeast, the mating-type region consists of three loci called mat1, mat2, and mat3. The mat2 and mat3 loci are always silent and only act as donors of genetic information required for switching the transcriptionally active mat1 locus. Studies on Silencing We previously found that silencing mechanism involves a chromosomally heritable epigenetic alteration, presumably of chromatin associated with the mat region. In collaboration with Dr. Shiv Grewal (a previous postdoc in our group) at Cold Spring Harbor Laboratory, we have discovered that swi6p performs imprinting function for silencing donor loci. Inheritance of stable states of gene expression is essential for cellular differentiation. In fission yeast, an epigenetic imprint marking the mating-type (mat2/3) region contributes to inheritance of the silenced state, but the nature of the imprint is not known. We show that a chromodomain-containing swi6 protein is a dosage-critical component involved in imprinting the mat locus. Transient overexpression of swi6p alters the epigenetic imprint at the mat2/3 region and heritably converts the expressed state to the silenced state. The establishment and maintenance of the imprint are tightly coupled to the recruitment and the persistence of swi6 at the mat2/3 region during mitosis as well as meiosis. Remarkably, swi6p remains bound to the mat2/3 interval throughout the cell and itself seems to be a component of the imprint. Our analyses suggest that the unit of inheritance at the mat2/3 locus comprises the DNA plus the associated swi6 protein complex. Interestingly the silenced domain is bracketed by 1.2KB inverted repeat sequences that block spreading of heterochromatin to adjoining regions of chromosome. Our work on will continues to define the genetic determinants of silencing. This work has direct implication for explaining eucaryotic cellular differentiation and for cancer development as disruption of epigenetic controls constitutes a prominant mechanism of unwanted cellular growth.
| Singh, Gurjeet; Klar, Amar J S (2008) Mutations in deoxyribonucleotide biosynthesis pathway cause spreading of silencing across heterochromatic barriers at the mating-type region of the fission yeast. Yeast 25:117-28 |
| Klar, Amar J S (2007) Lessons learned from studies of fission yeast mating-type switching and silencing. Annu Rev Genet 41:213-36 |
| Singh, Gurjeet; Klar, Amar J S (2003) DNA sequence of the mat2,3 region of Schizosaccharomyces kambucha shares high homology with the corresponding sequence from Sz. pombe. Yeast 20:1273-8 |
