Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila

Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome–nucleosome interactions and directly affects nucleosome binding by certain proteins. In Drosophila, H4K16 acetylation by the dosage compensation complex subunit Mof is linked to increased transcription of genes on the single X chrom...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2018-12, Vol.115 (52), p.13336-13341
Main Authors: Copur, Ömer, Gorchakov, Andrey, Finkl, Katja, Kuroda, Mitzi I., Müller, Jürg
Format: Article
Language:English
Subjects:
Acetylation
Adults
Animals
Biological Sciences
Chromatin
Chromosomes
Compensation
Dosage
Dosage compensation
Dosage Compensation, Genetic - genetics
Drosophila
Drosophila melanogaster - genetics
Drosophila Proteins - genetics
Embryos
Female
Females
Gastrulation
Genes
Genotype & phenotype
Genotypes
Histone Acetyltransferases - metabolism
Histone H4
Histones - genetics
Histones - metabolism
Lethality
Lysine
Lysine - genetics
Male
Males
MOF protein
Mutants
Mutation
Nuclear Proteins - metabolism
Nucleosomes - metabolism
Phenotype
Phenotypes
Point Mutation - genetics
Protein Processing, Post-Translational - genetics
Proteins
Sex
Sex Factors
Transcription
Transcription Factors - metabolism
X Chromosome - metabolism
X chromosomes
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Summary:Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome–nucleosome interactions and directly affects nucleosome binding by certain proteins. In Drosophila, H4K16 acetylation by the dosage compensation complex subunit Mof is linked to increased transcription of genes on the single X chromosome in males. Here, we analyzed Drosophila containing different H4K16 mutations or lacking Mof protein. An H4K16A mutation causes embryonic lethality in both sexes, whereas an H4K16R mutation permits females to develop into adults but causes lethality in males. The acetyl-mimic mutation H4K16Q permits both females and males to develop into adults. Complementary analyses reveal that males lacking maternally deposited and zygotically expressed Mof protein arrest development during gastrulation, whereas females of the same genotype develop into adults. Together, this demonstrates the causative role of H4K16 acetylation by Mof for dosage compensation in Drosophila and uncovers a previously unrecognized requirement for this process already during the onset of zygotic gene transcription.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1817274115