There are an infinite number of possible sublinear curves. If the nature of the dose response on the X chromosome differed from the autosomes, or the presence or absence of MSL, then scaling should not result in a common fit. However, if the three dose response selleck products curves are the result of a common dosage compensation mechanism, then they should scale to yield a single curve that fits all three of the absolute dose-response curves. We set median expression fold change at 2X and 4A to 1.0 for both copy number and expression (Figure 6C). We found that X chromosome and autosomes show remarkably similar fold changes in expression relative to fold changes in copy number. Additionally, the relationship between X chromosome expression and copy number is MSL independent following scaling.

These data suggest that like the autosomes, the X chromosome is subject to dosage compensation based on actual gene dose. The gene dose to expression response fits a one parameter model y=x(EC50 +1)/(EC50 + x), where y is transcript abundance, x is DNA copy number expressed as a ratio relative to wild type, and EC50 is the copy number required for half maximal expression (r2>0.99). This indicates that gene expression is a saturating function of gene dose regardless of chromosome location or the presence of MSL. Discussion Our data indicate that the MSL complex and general compensation mechanisms independently contribute to male X chromosome dosage compensation. The MSL complex recognizes active X chromosome genes [28]�C[31].

We have shown that MSL then acts as a simple unidirectional multiplier of expression regardless of the actual gene dose and gene expression level. In contrast, buffering and feed-back are dose sensitive and absorb the expression perturbations caused by unbalanced dose. We suggest that all these mechanisms are critical for proper X chromosome dosage compensation. Some rough accounting illustrates the composite nature of X chromosome dosage compensation. In the Drosophila genus, dosage compensation results in a 2.0- to 2.2-fold increase in X chromosome expression in males relative to autosomes [13],[32]. Similarly, in S2 cells we observed a 2.08-fold increase in X chromosome expression. The fixed-fold effect of MSL resulted in at least a 1.35-fold increase in X-chromosome expression. Dose-responsive compensation also acted to increase X chromosome expression and was independent of MSL function.

We can estimate the contribution of dose-responsive compensation from work performed on whole flies and on S2 cells. Autosomal dosage compensation increases per copy expression by 1.4- to 1.6-fold in diploid flies with a single copy of tens of genes [13],[19]. In agreement with Entinostat those reported values, we can project that a 2-fold change in scaled DNA dose in S2 cells results in about a 1.