The MOF Chromobarrel Domain Controls Genome-wide H4K16 Acetylation and Spreading of the MSL Complex

• Published in: Developmental cell 2012-03, Vol.22 (3), p.610-624
• Main Authors: Conrad, Thomas, Cavalli, Florence M.G., Holz, Herbert, Hallacli, Erinc, Kind, Jop, Ilik, Ibrahim, Vaquerizas, Juan M., Luscombe, Nicholas M., Akhtar, Asifa
• Format: Article
• Language: English
• Subjects: Acetylation; Acetyltransferase; Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Chromatin; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Dosage compensation; Drosophila; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila Proteins - chemistry; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enzymatic activity; Female; Fundamental and applied biological sciences. Psychology; Genome, Insect; Genomes; Histone Acetyltransferases - chemistry; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histone H4; Histones - genetics; Histones - metabolism; Lysine; Male; Molecular and cellular biology; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; nucleic acids; Nucleosomes; Protein Structure, Tertiary; Spreading; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism; X chromosome; X Chromosome - genetics; X Chromosome - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.12.016

The histone H4 lysine 16 (H4K16)-specific acetyltransferase MOF is part of two distinct complexes involved in X chromosome dosage compensation and autosomal transcription regulation. Here we show that the MOF chromobarrel domain is essential for H4K16 acetylation throughout the Drosophila genome and is required for spreading of the male-specific lethal (MSL) complex on the X chromosome. The MOF chromobarrel domain directly interacts with nucleic acids and potentiates MOF's enzymatic activity after chromatin binding, making it a unique example of a chromo-like domain directly controlling acetylation activity in vivo. We also show that the Drosophila-specific N terminus of MOF has evolved to perform sex-specific functions. It modulates nucleosome binding and HAT activity and controls MSL complex assembly, thus regulating MOF function in dosage compensation. We propose that MOF has been especially tailored to achieve tight regulation of its enzymatic activity and enable its dual role on X and autosomes. ► The MOF chromobarrel domain is required for spreading of the MSL complex ► The chromobarrel domain directly interacts with RNA and DNA ► The chromobarrel domain triggers MOF-mediated H4K16 acetylation ► MOF N terminus controls acetyltransferase activity and assembly of the MSL complex Conrad et al. show that the chromobarrel domain of the histone acetyltransferase MOF directly interacts with nucleic acids and triggers H4K16 acetylation. At the same time, the Drosophila-specific MOF N terminus modulates nucleosome binding and acetyltransferase activity and controls MSL complex assembly, thus regulating MOF function in X-chromosome dosage compensation.