What makes a histone variant a variant: Changing H2A to become H2A.Z.
Chromatin structure and underlying DNA accessibility is modulated by the incorporation of histone variants. H2A.Z, a variant of the H2A core histone family, plays a distinct and essential role in a diverse set of biological functions including gene regulation and maintenance of heterochromatin-euchr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-12-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009950&type=printable |
| _version_ | 1826554769654677504 |
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| author | Hilary T Brewis Alice Y Wang Aline Gaub Justine J Lau Peter C Stirling Michael S Kobor |
| author_facet | Hilary T Brewis Alice Y Wang Aline Gaub Justine J Lau Peter C Stirling Michael S Kobor |
| author_sort | Hilary T Brewis |
| collection | DOAJ |
| description | Chromatin structure and underlying DNA accessibility is modulated by the incorporation of histone variants. H2A.Z, a variant of the H2A core histone family, plays a distinct and essential role in a diverse set of biological functions including gene regulation and maintenance of heterochromatin-euchromatin boundaries. Although it is currently unclear how the replacement of H2A with H2A.Z can regulate gene expression, the variance in their amino acid sequence likely contributes to their functional differences. To tease apart regions of H2A.Z that confer its unique identity, a set of plasmids expressing H2A-H2A.Z hybrids from the native H2A.Z promoter were examined for their ability to recapitulate H2A.Z function. First, we found that the H2A.Z M6 region was necessary and sufficient for interaction with the SWR1-C chromatin remodeler. Remarkably, the combination of only 9 amino acid changes, the H2A.Z M6 region, K79 and L81 (two amino acids in the α2-helix), were sufficient to fully rescue growth phenotypes of the htz1Δ mutant. Furthermore, combining three unique H2A.Z regions (K79 and L81, M6, C-terminal tail) was sufficient for expression of H2A.Z-dependent heterochromatin-proximal genes and GAL1 derepression. Surprisingly, hybrid constructs that restored the transcription of H2A.Z-dependent genes, did not fully recapitulate patterns of H2A.Z-specific enrichment at the tested loci. This suggested that H2A.Z function in transcription regulation may be at least partially independent of its specific localization in chromatin. Together, this work has identified three regions that can confer specific H2A.Z-identity to replicative H2A, furthering our understanding of what makes a histone variant a variant. |
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| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2025-03-14T07:46:11Z |
| publishDate | 2021-12-01 |
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| series | PLoS Genetics |
| spelling | doaj.art-b7f2805cff804c39b8f709b9ccf8455d2025-03-03T05:32:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-12-011712e100995010.1371/journal.pgen.1009950What makes a histone variant a variant: Changing H2A to become H2A.Z.Hilary T BrewisAlice Y WangAline GaubJustine J LauPeter C StirlingMichael S KoborChromatin structure and underlying DNA accessibility is modulated by the incorporation of histone variants. H2A.Z, a variant of the H2A core histone family, plays a distinct and essential role in a diverse set of biological functions including gene regulation and maintenance of heterochromatin-euchromatin boundaries. Although it is currently unclear how the replacement of H2A with H2A.Z can regulate gene expression, the variance in their amino acid sequence likely contributes to their functional differences. To tease apart regions of H2A.Z that confer its unique identity, a set of plasmids expressing H2A-H2A.Z hybrids from the native H2A.Z promoter were examined for their ability to recapitulate H2A.Z function. First, we found that the H2A.Z M6 region was necessary and sufficient for interaction with the SWR1-C chromatin remodeler. Remarkably, the combination of only 9 amino acid changes, the H2A.Z M6 region, K79 and L81 (two amino acids in the α2-helix), were sufficient to fully rescue growth phenotypes of the htz1Δ mutant. Furthermore, combining three unique H2A.Z regions (K79 and L81, M6, C-terminal tail) was sufficient for expression of H2A.Z-dependent heterochromatin-proximal genes and GAL1 derepression. Surprisingly, hybrid constructs that restored the transcription of H2A.Z-dependent genes, did not fully recapitulate patterns of H2A.Z-specific enrichment at the tested loci. This suggested that H2A.Z function in transcription regulation may be at least partially independent of its specific localization in chromatin. Together, this work has identified three regions that can confer specific H2A.Z-identity to replicative H2A, furthering our understanding of what makes a histone variant a variant.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009950&type=printable |
| spellingShingle | Hilary T Brewis Alice Y Wang Aline Gaub Justine J Lau Peter C Stirling Michael S Kobor What makes a histone variant a variant: Changing H2A to become H2A.Z. PLoS Genetics |
| title | What makes a histone variant a variant: Changing H2A to become H2A.Z. |
| title_full | What makes a histone variant a variant: Changing H2A to become H2A.Z. |
| title_fullStr | What makes a histone variant a variant: Changing H2A to become H2A.Z. |
| title_full_unstemmed | What makes a histone variant a variant: Changing H2A to become H2A.Z. |
| title_short | What makes a histone variant a variant: Changing H2A to become H2A.Z. |
| title_sort | what makes a histone variant a variant changing h2a to become h2a z |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009950&type=printable |
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