title: Cellular resolution maps of X chromosome inactivation: implications for neural development, function, and disease.
abstract: Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from ∼4% of the genome. To quantitatively map the topography of XCI for defined cell types at single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters--GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific, genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Rattner
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Alisa
authors.initials: A
authors.lastname: Mo
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Smallwood
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Bracha
authors.initials: B
authors.lastname: Erlanger
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wheelan
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jnathans@jhmi.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012160:Retina / Q000166:cytology; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase