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.
Highlights
The intricate regulation of gene expression that occurs in all organisms is the result of the coordinated activity of multiple machineries (RNA Polymerases, transcription factors, histone modifiers, chromatin modifiers, etc.)
The dosage compensation complex (DCC) is comprised of a regulatory subcomplex composed of SDC-1, SDC-2, SDC-3, DPY-30, and DPY-21, and an enzymatic condensin complex comprised of DPY-27, MIX-1, CAPG-1, DPY-28, and DPY-26, similar to mitotic and meiotic condensin complexes [1,4]
Previously we have shown that the H2A.Z variant in C. elegans (HTZ-1) plays a role in regulating DCC targeting to the X chromosomes [23]
Summary
The intricate regulation of gene expression that occurs in all organisms is the result of the coordinated activity of multiple machineries (RNA Polymerases, transcription factors, histone modifiers, chromatin modifiers, etc.). In order for this to be achieved, these machineries need to be targeted to very specific sites of action within the vast expanse of the genome. We discuss the targeting of a specialized gene regulatory complex in C. elegans called the dosage compensation complex (DCC) In organisms such as C. elegans, the difference in sex chromosome number between the sexes, if left uncorrected, would result in an imbalance of X-linked gene expression in the affected sex. SDC-2 and SDC-3 can bind to chromatin independent of the condensin complex but the reverse is not true [5,6,7]
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