Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Copur, Ömer, Gorchakov, Andrey, Finkl, Katja, Kuroda, Mitzi I., Müller, Jürg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310812/
https://www.ncbi.nlm.nih.gov/pubmed/30530664
http://dx.doi.org/10.1073/pnas.1817274115
_version_ 1783383498186293248
author Copur, Ömer
Gorchakov, Andrey
Finkl, Katja
Kuroda, Mitzi I.
Müller, Jürg
author_facet Copur, Ömer
Gorchakov, Andrey
Finkl, Katja
Kuroda, Mitzi I.
Müller, Jürg
author_sort Copur, Ömer
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6310812
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-63108122019-01-04 Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila Copur, Ömer Gorchakov, Andrey Finkl, Katja Kuroda, Mitzi I. Müller, Jürg Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2018-12-26 2018-12-10 /pmc/articles/PMC6310812/ /pubmed/30530664 http://dx.doi.org/10.1073/pnas.1817274115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Copur, Ömer
Gorchakov, Andrey
Finkl, Katja
Kuroda, Mitzi I.
Müller, Jürg
Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title_full Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title_fullStr Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title_full_unstemmed Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title_short Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila
title_sort sex-specific phenotypes of histone h4 point mutants establish dosage compensation as the critical function of h4k16 acetylation in drosophila
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310812/
https://www.ncbi.nlm.nih.gov/pubmed/30530664
http://dx.doi.org/10.1073/pnas.1817274115
work_keys_str_mv AT copuromer sexspecificphenotypesofhistoneh4pointmutantsestablishdosagecompensationasthecriticalfunctionofh4k16acetylationindrosophila
AT gorchakovandrey sexspecificphenotypesofhistoneh4pointmutantsestablishdosagecompensationasthecriticalfunctionofh4k16acetylationindrosophila
AT finklkatja sexspecificphenotypesofhistoneh4pointmutantsestablishdosagecompensationasthecriticalfunctionofh4k16acetylationindrosophila
AT kurodamitzii sexspecificphenotypesofhistoneh4pointmutantsestablishdosagecompensationasthecriticalfunctionofh4k16acetylationindrosophila
AT mullerjurg sexspecificphenotypesofhistoneh4pointmutantsestablishdosagecompensationasthecriticalfunctionofh4k16acetylationindrosophila