title: SFRS7-mediated splicing of tau exon 10 is directly regulated by STOX1A in glial cells.
abstract: BACKGROUND
  In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer's disease and affecting the amyloid processing pathway.
  
  
  RESULTS
  Our results show that out of 218 genes bound by STOX1A as identified by chromatin-immunoprecipitation followed by sequencing (ChIP-Seq), the serine/arginine-rich splicing factor 7 (SFRS7) was found to be induced, both at the mRNA and protein levels, by STOX1A after stable transfection in glial cells. The increase in SFRS7 was followed by an increase in the 4R/3R ratios of the microtubule-associated protein tau (MAPT) by differential exon 10 splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration.
  
  
  CONCLUSIONS
  Our data further supports the functional importance and central role of STOX1A in neurodegeneration.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: van Abel
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Hölzel
authors.forename: Shushant
authors.initials: S
authors.lastname: Jain
authors.forename: Fiona M F
authors.initials: FM
authors.lastname: Lun
authors.forename: Yama W L
authors.initials: YW
authors.lastname: Zheng
authors.forename: Eric Z
authors.initials: EZ
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
authors.forename: Y M Dennis
authors.initials: YM
authors.lastname: Lo
authors.forename: Marie
authors.initials: M
authors.lastname: van Dijk
authors.forename: Cees B M
authors.initials: CB
authors.lastname: Oudejans
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009457:Neuroglia / Q000378:metabolism*; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D000068103:Serine-Arginine Splicing Factors; D014162:Transfection; D016875:tau Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C500784:STOX1 protein, human; D016875:tau Proteins; D000068103:Serine-Arginine Splicing Factors; D004247:DNA