title: The essential Drosophila CLAMP protein differentially regulates non-coding roX RNAs in male and females.
abstract: Heterogametic species require chromosome-wide gene regulation to compensate for differences in sex chromosome gene dosage. In Drosophila melanogaster, transcriptional output from the single male X-chromosome is equalized to that of XX females by recruitment of the male-specific lethal (MSL) complex, which increases transcript levels of active genes 2-fold. The MSL complex contains several protein components and two non-coding RNA on the X ( roX) RNAs that are transcriptionally activated by the MSL complex. We previously discovered that targeting of the MSL complex to the X-chromosome is dependent on the chromatin-linked adapter for MSL proteins (CLAMP) zinc finger protein. To better understand CLAMP function, we used the CRISPR/Cas9 genome editing system to generate a frameshift mutation in the clamp gene that eliminates expression of the CLAMP protein. We found that clamp null females die at the third instar larval stage, while almost all clamp null males die at earlier developmental stages. Moreover, we found that in clamp null females roX gene expression is activated, whereas in clamp null males roX gene expression is reduced. Therefore, CLAMP regulates roX abundance in a sex-specific manner. Our results provide new insights into sex-specific gene regulation by an essential transcription factor.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Urban
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.|Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Doherty
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Jordan
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Bliss
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.|University of Massachusetts Medical School, Worcester, MA, 01655, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.|LGC Biosearch Technologies, Petaluma, CA, 94954, USA.
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Soruco
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors.forename: Leila E
authors.initials: LE
authors.lastname: Rieder
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tsiarli
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA. Erica_Larschan@Brown.edu.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Larschan
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D009687:Nuclear Proteins / Q000502:physiology*; D022661:RNA, Untranslated; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014960:X Chromosome / Q000235:genetics*
chemical_list: C583531:CLAMP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D022661:RNA, Untranslated; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C454144:roX1 protein, Drosophila
keywords: Drosophila; dosage compensation; gene regulation; transcription factor