title: Condensin complexes regulate mitotic progression and interphase chromatin structure in embryonic stem cells.
abstract: In an RNA interference screen interrogating regulators of mouse embryonic stem (ES) cell chromatin structure, we previously identified 62 genes required for ES cell viability. Among these 62 genes were Smc2 and -4, which are core components of the two mammalian condensin complexes. In this study, we show that for Smc2 and -4, as well as an additional 49 of the 62 genes, knockdown (KD) in somatic cells had minimal effects on proliferation or viability. Upon KD, Smc2 and -4 exhibited two phenotypes that were unique to ES cells and unique among the ES cell-lethal targets: metaphase arrest and greatly enlarged interphase nuclei. Nuclear enlargement in condensin KD ES cells was caused by a defect in chromatin compaction rather than changes in DNA content. The altered compaction coincided with alterations in the abundance of several epigenetic modifications. These data reveal a unique role for condensin complexes in interphase chromatin compaction in ES cells.
authors.affiliation: Biochemistry and Biophysics Department, University of California, San Francisco, San Francisco, CA 94158, USA. thomas.fazzio@ucsf.edu
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Fazzio
authors.forename: Barbara
authors.initials: B
authors.lastname: Panning
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000705:Anaphase; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D002843:Chromatin / Q000737:chemistry*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D007399:Interphase; D008677:Metaphase; D051379:Mice; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D016159:Tumor Suppressor Protein p53; C108312:condensin complexes; D012694:Serine; D000251:Adenosine Triphosphatases