Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in XXXX .

@entity72420 @entity2199 @entity19 @entity66029 @entity51575 @entity66028
UNASSIGNED: In @entity2199 , 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 H4K20 @entity19 between 100-cell to comma stage. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of @entity72420 (condensin subunit), @entity51575 (non-condensin DCC member), @entity66028 (H4K20 monomethylase) and @entity66029 (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. @entity72420 and @entity51575 are required for X chromosome repression throughout development, but particularly in early embryos @entity72420 and @entity51575 mutations produced distinct expression changes, suggesting a DCC independent role for @entity51575 . We previously hypothesized that the DCC increases H4K20me1 by reducing @entity66029 activity on the X chromosomes. Accordingly, in the @entity66029 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 @entity66028 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the @entity66029 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes only slightly to X-repression. Thus H4K20me1 by itself is not a downstream effector of the DCC. 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.
