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Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans.
PLoS Genet 2015; 11(12):e1005698PG

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+Show Affiliations

Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26641248

Citation

Kramer, Maxwell, et al. "Developmental Dynamics of X-Chromosome Dosage Compensation By the DCC and H4K20me1 in C. Elegans." PLoS Genetics, vol. 11, no. 12, 2015, pp. e1005698.
Kramer M, Kranz AL, Su A, et al. Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. PLoS Genet. 2015;11(12):e1005698.
Kramer, M., Kranz, A. L., Su, A., Winterkorn, L. H., Albritton, S. E., & Ercan, S. (2015). Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. PLoS Genetics, 11(12), pp. e1005698. doi:10.1371/journal.pgen.1005698.
Kramer M, et al. Developmental Dynamics of X-Chromosome Dosage Compensation By the DCC and H4K20me1 in C. Elegans. PLoS Genet. 2015;11(12):e1005698. PubMed PMID: 26641248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. AU - Kramer,Maxwell, AU - Kranz,Anna-Lena, AU - Su,Amanda, AU - Winterkorn,Lara H, AU - Albritton,Sarah Elizabeth, AU - Ercan,Sevinc, Y1 - 2015/12/07/ PY - 2015/05/07/received PY - 2015/11/03/accepted PY - 2015/12/8/entrez PY - 2015/12/8/pubmed PY - 2016/6/2/medline SP - e1005698 EP - e1005698 JF - PLoS genetics JO - PLoS Genet. VL - 11 IS - 12 N2 - 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/26641248/Developmental_Dynamics_of_X_Chromosome_Dosage_Compensation_by_the_DCC_and_H4K20me1_in_C__elegans_ L2 - http://dx.plos.org/10.1371/journal.pgen.1005698 DB - PRIME DP - Unbound Medicine ER -