title: Noncoding Transcription Is a Driving Force for Nucleosome Instability in spt16 Mutant Cells.
abstract: FACT (facilitates chromatin transcription) consists of two essential subunits, Spt16 and Pob3, and functions as a histone chaperone. Mutation of spt16 results in a global loss of nucleosomes as well as aberrant transcription. Here, we show that the majority of nucleosome changes upon Spt16 depletion are alterations in nucleosome fuzziness and position shift. Most nucleosomal changes are suppressed by the inhibition of RNA polymerase II (Pol II) activity. Surprisingly, a small subgroup of nucleosome changes is resistant to transcriptional inhibition. Notably, Spt16 and distinct histone modifications are enriched at this subgroup of nucleosomes. We also report 1,037 Spt16-suppressed noncoding transcripts (SNTs) and found that the SNT start sites are enriched with the subgroup of nucleosomes resistant to Pol II inhibition. Finally, the nucleosomes at genes overlapping SNTs are more susceptible to changes upon Spt16 depletion than those without SNTs. Taken together, our results support a model in which Spt16 has a role in maintaining local nucleosome stability to inhibit initiation of SNT transcription, which once initiated drives additional nucleosome loss upon Spt16 depletion.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Gan
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Eaton
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Belsky
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: MacAlpine
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA Zhang.Zhiguo@mayo.edu li.qing@pku.edu.cn.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China Zhang.Zhiguo@mayo.edu li.qing@pku.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
mesh_terms: D009154:Mutation; D009707:Nucleosomes / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics*
chemical_list: D009707:Nucleosomes; C071238:SPT16 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II