title: Analysis of epigenetic alterations to proprotein convertase genes in disease.
abstract: Epigenetic alterations produce heritable changes in phenotype or gene expression without changing DNA sequence. Modified levels of gene expression contribute to a variety of human diseases encompassing genetic disorders, pediatric syndromes, autoimmune disease, aging, and cancer. Alterations in proprotein convertase gene expression are associated with numerous disease states; however, the underlying mechanism for changes in PC gene expression remains understudied. Epigenetic changes in gene expression profiles can be accomplished through modification of chromatin, specifically via chemical modification of DNA bases (methylation of cytosine) or associated histone proteins (acetylation or methylation). In general, active chromatin is associated with low DNA methylation status and histone acetylation, whereas silenced gene are typically in inactive regions of chromatin exhibiting DNA hypermethylation and histone deacetylation. This chapter will provide in-depth protocols to analyze epigenetic alterations in proprotein convertase gene expression using the PCSK6 gene in the context of human ovarian cancer as a model system.
authors.affiliation: Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada. yangxin@ualberta.ca
authors.forename: YangXin
authors.initials: Y
authors.lastname: Fu
authors.forename: Mark W
authors.initials: MW
authors.lastname: Nachtigal
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D005819:Genetic Markers; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013447:Sulfites / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D002843:Chromatin; D005819:Genetic Markers; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D013447:Sulfites; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases