Activation of Transcription through Histone H4 Acetylation by MOF, an Acetyltransferase Essential for Dosage Compensation in Drosophila

TLDR

Dosage compensation in Drosophila upregulates transcription from the single male X chromosome twofold, a process linked to chromatin decondensation and H4K16 acetylation. The study aims to show that MOF, a MYST‑family protein essential for dosage compensation, functions as a histone acetyltransferase targeting H4K16. MOF acetylates chromatin specifically at H4K16, as demonstrated by in vitro and in vivo assays. Acetylation of H4K16 by MOF relieves chromatin repression and activates transcription, establishing a causal role for MOF‑mediated acetylation in dosage compensation.

Abstract

Dosage compensation in Drosophila involves a 2-fold increase in transcription from the single male X relative to the two female X chromosomes. Regulation at the level of the chromosome involves alterations in chromatin organization: male X chromosomes appear decondensed and are marked by acetylation of histone H4 at lysine 16. We demonstrate that MOF, a protein required for dosage compensation with significant sequence similarity to the MYST family of acetyltransferases, is a histone acetyltransferase that acetylates chromatin specifically at histone H4 lysine 16. This acetylation relieves chromatin-mediated repression of transcription in vitro and in vivo if MOF is targeted to a promoter by fusion to a DNA-binding domain. Acetylation of chromatin by MOF, therefore, appears to be causally involved in transcriptional activation during dosage compensation.