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epigenetics, epigenomics, chromatin
RESEARCH
Epigenetics is the study of heritable changes in phenotype that occur without changes in DNA sequence. Epigenetic mechanisms are essential for many cellular processes, such as gene-expression regulation, genome organization and cell-fate determination. Defects in epigenetic regulation have been implicated in a variety of diseases, including cancer. The aim of our research is to understand the fundamental principles of epigenetic regulation. Toward this goal, we have chosen to study the fission yeast (Schizosaccharomyces pombe), a model eukaryotic organism well suited to a combination of powerful experimental approaches, including genetics, cell biology, biochemistry and genomics. Importantly, fission yeast contains many conserved epigenetic components, and has thus emerged as a premier model for epigenetic study.
Epigenetic Regulation of Heterochromatin
In eukaryotes, DNA is packaged together with histone proteins into an ordered, highly complex chromatin structure. Chromatin exists in two forms: euchromatin and heterochromatin. Euchromatin is typically transcriptionally active and loosely packaged, whereas heterochromatin is gene-poor and appears highly compact throughout the cell cycle. Heterochromatin is a classic example of epigenetic phenomena and plays an important role in gene regulation, chromosome segregation and genome stability. Taking advantage of powerful genetic and biochemical approaches available in fission yeast, we have identified multiple key heterochromatin factors. We aim to understand the epigenetic mechanisms that regulate establishment and maintenance of heterochromatin.
Epigenetic Regulation of Centromeres
Centromeres are specific chromosomal loci where the kinetochore, a multiprotein complex, is assembled. Kinetochores mediate attachment of spindle microtubules to centromeres, ensuring proper segregation of chromosomes during mitosis and meiosis. A fundamental question in biology is how centromere identity is defined and maintained through generations. In most eukaryotes, centromere assembly and propagation are regulated by epigenetic mechanisms. Centromere Protein-A (CENP-A), a centromere-specific histone 3 variant, represents the most likely candidate for the epigenetic mark that specifies centromere identity. CENP-A provides a structural and functional foundation for the assembly of kinetochores. Defects in the regulation of CENP-A are catastrophic for cells and result in chromosome mis-segregation and aneuploidy, or an abnormal number of chromosomes, the hallmark of human cancers. We are currently using biochemical, genetic, cytological and genomic approaches to dissect the gene regulatory network mediating the faithful inheritance of centromeres.
epigenetics, epigenomics, chromatin
RESEARCH
Epigenetics is the study of heritable changes in phenotype that occur without changes in DNA sequence. Epigenetic mechanisms are essential for many cellular processes, such as gene-expression regulation, genome organization and cell-fate determination. Defects in epigenetic regulation have been implicated in a variety of diseases, including cancer. The aim of our research is to understand the fundamental principles of epigenetic regulation. Toward this goal, we have chosen to study the fission yeast (Schizosaccharomyces pombe), a model eukaryotic organism well suited to a combination of powerful experimental approaches, including genetics, cell biology, biochemistry and genomics. Importantly, fission yeast contains many conserved epigenetic components, and has thus emerged as a premier model for epigenetic study.
Epigenetic Regulation of Heterochromatin
In eukaryotes, DNA is packaged together with histone proteins into an ordered, highly complex chromatin structure. Chromatin exists in two forms: euchromatin and heterochromatin. Euchromatin is typically transcriptionally active and loosely packaged, whereas heterochromatin is gene-poor and appears highly compact throughout the cell cycle. Heterochromatin is a classic example of epigenetic phenomena and plays an important role in gene regulation, chromosome segregation and genome stability. Taking advantage of powerful genetic and biochemical approaches available in fission yeast, we have identified multiple key heterochromatin factors. We aim to understand the epigenetic mechanisms that regulate establishment and maintenance of heterochromatin.
Epigenetic Regulation of Centromeres
Centromeres are specific chromosomal loci where the kinetochore, a multiprotein complex, is assembled. Kinetochores mediate attachment of spindle microtubules to centromeres, ensuring proper segregation of chromosomes during mitosis and meiosis. A fundamental question in biology is how centromere identity is defined and maintained through generations. In most eukaryotes, centromere assembly and propagation are regulated by epigenetic mechanisms. Centromere Protein-A (CENP-A), a centromere-specific histone 3 variant, represents the most likely candidate for the epigenetic mark that specifies centromere identity. CENP-A provides a structural and functional foundation for the assembly of kinetochores. Defects in the regulation of CENP-A are catastrophic for cells and result in chromosome mis-segregation and aneuploidy, or an abnormal number of chromosomes, the hallmark of human cancers. We are currently using biochemical, genetic, cytological and genomic approaches to dissect the gene regulatory network mediating the faithful inheritance of centromeres.
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