title: Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.
abstract: Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.|Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Guray
authors.identifier: 0000-0002-7910-5985
authors.initials: G
authors.lastname: Kuzu
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Kaye
authors.affiliation: Department of Cell Biology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chery
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Trevor
authors.initials: T
authors.lastname: Siggers
authors.affiliation: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Lin
authors.identifier: 0000-0001-9155-6386
authors.initials: L
authors.lastname: Yang
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Jason R
authors.identifier: 0000-0002-2306-2250
authors.initials: JR
authors.lastname: Dobson
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Sonia
authors.initials: S
authors.lastname: Boor
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Bliss
authors.affiliation: Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Gerwald
authors.initials: G
authors.lastname: Jogl
authors.affiliation: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Nadia D
authors.initials: ND
authors.lastname: Singh
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tolstorukov
authors.affiliation: Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Erica
authors.initials: E
authors.lastname: Larschan
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D018900:Dinucleotide Repeats; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D050172:Genes, X-Linked; D008040:Genetic Linkage; D049750:Genome, Insect; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA; D014960:X Chromosome / Q000235:genetics*
chemical_list: C583531:CLAMP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004247:DNA