title: Regulation of DCC localization by HTZ-1/H2A.Z and DPY-30 does not correlate with H3K4 methylation levels.
abstract: Dosage compensation is a specialized form of gene regulation that balances sex-chromosome linked gene expression between the sexes. In C. elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC binds along both X chromosomes in hermaphrodites to down-regulate gene expression by half, limiting X-linked gene products to levels produced in XO males. Sequence motifs enriched on the X chromosome play an important role in targeting the DCC to the X. However, these motifs are not strictly X-specific and therefore other factors, such as the chromatin environment of the X chromosome, are likely to aid in DCC targeting. Previously, we found that loss of HTZ-1 results in partial disruption of dosage compensation localization to the X chromosomes. We wanted to know whether other chromatin components coordinated with HTZ-1 to regulate DCC localization. One candidate is DPY-30, a protein known to play a role in DCC localization. DPY-30 homologs in yeast, flies, and mammals are highly conserved members of histone H3 lysine 4 (H3K4) methyltransferase Set1/MLL complexes. Therefore, we investigated the hypothesis that the dosage compensation function of DPY-30 involves H3K4 methylation. We found that in dpy-30 animals the DCC fails to stably bind chromatin. Interestingly, of all the C. elegans homologs of Set1/MLL complex subunits, only DPY-30 is required for stable DCC binding to chromatin. Additionally, loss of H3K4 methylation does not enhance DCC mislocalization in htz-1 animals. We conclude that DPY-30 and HTZ-1 have unique functions in DCC localization, both of which are largely independent of H3K4 methylation.
authors: Department of Molecular, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Emily
authors: E
authors: Petty
authors: Emily
authors: E
authors: Laughlin
authors: Györgyi
authors: G
authors: Csankovszki
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004303:Dosage Compensation, Genetic / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008239:Lysine; D008297:Male; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C096340:dpy-30 protein, C elegans; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine