Possible mechanisms for dosage compensation. (a) The twofold activation of the single male X chromosome in Drosophila could be achieved by a large, MOF-dependent activation of transcription through H4K16 acetylation and its counteraction by yet unknown factors, mediated by the dosage-compensation complex in males . In (a,b), transcriptional level 1 refers to the normal regulated level of transcription from a single uncompensated X chromosome in females. (b) Furthermore, the twofold activation of the male X chromosome could be achieved by a combination of mechanisms: a general buffering/feedback component and a dedicated feed-forward mechanism (dosage compensation as suggested in (a)) . The effects of these two processes could add up to the expected twofold compensation required to equalize the expression of X-linked genes between the sexes. (c) Precise transcription levels could result from negotiation between a number of activating and repressive factors (up and down arrows). In this instance, transcriptional level 1 refers to a 'basal' transcription state. This hypothetical model assumes that additional factors beyond those mentioned in (a) and (b) contribute to final transcription levels, such as male-enriched protein kinases, heterochromatin components, chromatin remodelers, and others (for details, see text).