title: Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans.
abstract: In Caenorhabditis elegans, the dosage compensation complex (DCC) specifically binds to and represses transcription from both X chromosomes in hermaphrodites. The DCC is composed of an X-specific condensin complex that interacts with several proteins. During embryogenesis, DCC starts localizing to the X chromosomes around the 40-cell stage, and is followed by X-enrichment of H4K20me1 between 100-cell to comma stage. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of dpy-27 (condensin subunit), dpy-21 (non-condensin DCC member), set-1 (H4K20 monomethylase) and set-4 (H4K20 di-/tri-methylase) in X chromosome repression using mRNA-seq and ChIP-seq analyses across several developmental time points. We found that the DCC starts repressing the X chromosomes by the 40-cell stage, but X-linked transcript levels remain significantly higher in hermaphrodites compared to males through the comma stage of embryogenesis. Dpy-27 and dpy-21 are required for X chromosome repression throughout development, but particularly in early embryos dpy-27 and dpy-21 mutations produced distinct expression changes, suggesting a DCC independent role for dpy-21. We previously hypothesized that the DCC increases H4K20me1 by reducing set-4 activity on the X chromosomes. Accordingly, in the set-4 mutant, H4K20me1 increased more from the autosomes compared to the X, equalizing H4K20me1 level between X and autosomes. H4K20me1 increase on the autosomes led to a slight repression, resulting in a relative effect of X derepression. H4K20me1 depletion in the set-1 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the set-4 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes slightly to X-repression. Thus H4K20me1 is not only a downstream effector of the DCC [corrected].In summary, X chromosome dosage compensation starts in early embryos as the DCC localizes to the X, and is strengthened in later embryogenesis by H4K20me1.
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Kranz
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Su
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Lara H
authors.initials: LH
authors.lastname: Winterkorn
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Sarah Elizabeth
authors.initials: SE
authors.lastname: Albritton
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
authors.forename: Sevinc
authors.initials: S
authors.lastname: Ercan
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004303:Dosage Compensation, Genetic; D047108:Embryonic Development; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002843:Chromatin; C584037:DPY-21 protein, C elegans; C090454:DPY-27 protein, C elegans; D009687:Nuclear Proteins; D011495:Histone-Lysine N-Methyltransferase; C577070:SET-4 protein, C elegans; C464501:Set-1 protein, C elegans