Condensin complexes regulate mitotic progression and interphase chromatin structure in embryonic stem cells.
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.
Fazzio
Thomas G
TG
Biochemistry and Biophysics Department, University of California, San Francisco, San Francisco, CA 94158, USA. thomas.fazzio@ucsf.edu
Panning
Barbara
B
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
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D016159:Tumor Suppressor Protein p53; C108312:condensin complexes; D012694:Serine; D000251:Adenosine Triphosphatases