title: YY1 binding association with sex-biased transcription revealed through X-linked transcript levels and allelic binding analyses.
abstract: Sex differences in susceptibility and progression have been reported in numerous diseases. Female cells have two copies of the X chromosome with X-chromosome inactivation imparting mono-allelic gene silencing for dosage compensation. However, a subset of genes, named escapees, escape silencing and are transcribed bi-allelically resulting in sexual dimorphism. Here we conducted in silico analyses of the sexes using human datasets to gain perspectives into such regulation. We identified transcription start sites of escapees (escTSSs) based on higher transcription levels in female cells using FANTOM5 CAGE data. Significant over-representations of YY1 transcription factor binding motif and ChIP-seq peaks around escTSSs highlighted its positive association with escapees. Furthermore, YY1 occupancy is significantly biased towards the inactive X (Xi) at long non-coding RNA loci that are frequent contacts of Xi-specific superloops. Our study suggests a role for YY1 in transcriptional activity on Xi in general through sequence-specific binding, and its involvement at superloop anchors.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Graduate Program in Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Graduate Program in Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Balaton
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Matthews
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Arenillas
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mathelier
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan.|RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.|Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, the University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Brown
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Wyeth W
authors.initials: WW
authors.lastname: Wasserman
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003198:Computer Simulation; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*; D012737:Sex Factors; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D049951:X Chromosome Inactivation / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; D050986:YY1 Transcription Factor