title: Mutation of histone H3 serine 86 disrupts GATA factor Ams2 expression and precise chromosome segregation in fission yeast.
abstract: Eukaryotic genomes are packed into discrete units, referred to as nucleosomes, by organizing around scaffolding histone proteins. The interplay between these histones and the DNA can dynamically regulate the function of the chromosomal domain. Here, we interrogated the function of a pair of juxtaposing serine residues (S86 and S87) that reside within the histone fold of histone H3. We show that fission yeast cells expressing a mutant histone H3 disrupted at S86 and S87 (hht2-S86AS87A) exhibited unequal chromosome segregation, disrupted transcriptional silencing of centromeric chromatin, and reduced expression of Ams2, a GATA-factor that regulates localization of the centromere-specific histone H3 variant CENP-A. We found that overexpression of ams2(+) could suppress the chromosome missegregation phenotype that arose in the hht2-S86AS87A mutant. We further demonstrate that centromeric localization of SpCENP-A(cnp1-1) was significantly compromised in hht2-S86AS87A, suggesting synergism between histone H3 and the centromere-targeting domain of SpCENP-A. Taken together, our work presents evidence for an uncharacterized serine residue in fission yeast histone H3 that affects centromeric integrity via regulating the expression of the SpCENP-A-localizing Ams2 protein. [173/200 words].
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Kim Kiat
authors.initials: KK
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Terenze Yao Rui
authors.initials: TY
authors.lastname: Ong
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Yue Rong
authors.initials: YR
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Eugene Guorong
authors.initials: EG
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Kwi Shan
authors.initials: KS
authors.lastname: Seah
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Chemical &Life Sciences, Nanyang Polytechnic, Singapore.
authors.forename: Tsu Soo
authors.initials: TS
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Dymock
authors.affiliation: Department of Biochemistry, School of Medicine, National University of Singapore, Singapore.|National University Health System (NUHS), National University of Singapore, Singapore.|Synthetic Biology Research Consortium, National University of Singapore, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Ee Sin
authors.initials: ES
authors.lastname: Chen
mesh_terms: D019943:Amino Acid Substitution; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D000066630:Ectopic Gene Expression; D050980:GATA Transcription Factors / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D014176:Protein Biosynthesis; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C472167:Ams2 protein, S pombe; D050980:GATA Transcription Factors; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins