role of the transcriptional corepressor bcor in embryonic stem cell differentiation and early embryonic development作用的转录辅阻遏物bcor在胚胎干细胞的分化和胚胎发育早期.pdfVIP

Role of the Transcriptional Corepressor Bcor in Embryonic Stem Cell Differentiation and Early Embryonic Development 1 2 3 1,2 Joseph Alan Wamstad , Connie Marie Corcoran , Anne Marjorie Keating , Vivian J. Bardwell * 1 Molecular, Cellular, Developmental Biology and Genetics Graduate Program, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Department of Genetics, Cell Biology and Development and Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Biochemistry, Molecular Biology and Biophysics Graduate Program, University of Minnesota, Minneapolis, Minnesota, United States of America Abstract Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase. To model OFCD in mice and dissect the role of Bcor in development we have characterized two loss of function Bcor alleles. We find that Bcor loss of function results in a strong parent-of-origin effect, most likely indicating a requirement for Bcor in extraembryonic development. Using Bcor loss of function embryonic stem (ES) cells and in vitro differentiation assays, we demonstrate that Bcor plays a role in the regulation of gene expression very early in the differentiation of ES cells into ectoderm, mesoderm and downstream hematopoietic lineages. Normal expression of affected genes (Oct3/4, Nanog, Fgf5, Bmp