Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway
Elongator dysfunction is increasingly recognized as a contributor to multiple neurodevelopmental and neurodegenerative disorders including familial dysautonomia, intellectual disability, amyotrophic lateral sclerosis, and autism spectrum disorder. Although numerous cellular processes are perturbed i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2021-09-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/10/9/bio058979 |
| _version_ | 1818402321595367424 |
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| author | BreAnna Cameron Elin Lehrmann Tien Chih Joseph Walters Richard Buksch Sara Snyder Joy Goffena Frances Lefcort Kevin G. Becker Lynn George |
| author_facet | BreAnna Cameron Elin Lehrmann Tien Chih Joseph Walters Richard Buksch Sara Snyder Joy Goffena Frances Lefcort Kevin G. Becker Lynn George |
| author_sort | BreAnna Cameron |
| collection | DOAJ |
| description | Elongator dysfunction is increasingly recognized as a contributor to multiple neurodevelopmental and neurodegenerative disorders including familial dysautonomia, intellectual disability, amyotrophic lateral sclerosis, and autism spectrum disorder. Although numerous cellular processes are perturbed in the context of Elongator loss, converging evidence from multiple studies has resolved Elongator's primary function in the cell to the modification of tRNA wobble uridines and the translational regulation of codon-biased genes. Here we characterize H2a.z, encoding the variant H2a histone H2A.Z, as an indirect Elongator target. We further show that canonical Notch signaling, a pathway directed by H2A.Z, is perturbed as a consequence of Elp1 loss. Finally, we demonstrate that hyperacetylation of H2A.Z and other histones via exposure to the histone deacetylase inhibitor Trichostatin A during neurogenesis corrects the expression of Notch3 and rescues the development of sensory neurons in embryos lacking the Elp1 Elongator subunit. |
| first_indexed | 2024-12-14T08:06:30Z |
| format | Article |
| id | doaj.art-f10f606d983743c4bc6ad48340bb8bb1 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-14T08:06:30Z |
| publishDate | 2021-09-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-f10f606d983743c4bc6ad48340bb8bb12022-12-21T23:10:10ZengThe Company of BiologistsBiology Open2046-63902021-09-0110910.1242/bio.058979058979Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathwayBreAnna Cameron0Elin Lehrmann1Tien Chih2Joseph Walters3Richard Buksch4Sara Snyder5Joy Goffena6Frances Lefcort7Kevin G. Becker8Lynn George9 Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Computational Biology & Genomics Core (CBGC), Laboratory of Genetics and Genomics (LGG), Department of Health and Human Services (DHHS), National Institute on Aging, Intramural Research Program (NIA IRP), National Institutes of Health (NIH), Biomedical Research Center, Baltimore, MD 21224, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA Department of Biological and Physical Sciences, Montana State University Billings, Billings, MT 59101, USA Elongator dysfunction is increasingly recognized as a contributor to multiple neurodevelopmental and neurodegenerative disorders including familial dysautonomia, intellectual disability, amyotrophic lateral sclerosis, and autism spectrum disorder. Although numerous cellular processes are perturbed in the context of Elongator loss, converging evidence from multiple studies has resolved Elongator's primary function in the cell to the modification of tRNA wobble uridines and the translational regulation of codon-biased genes. Here we characterize H2a.z, encoding the variant H2a histone H2A.Z, as an indirect Elongator target. We further show that canonical Notch signaling, a pathway directed by H2A.Z, is perturbed as a consequence of Elp1 loss. Finally, we demonstrate that hyperacetylation of H2A.Z and other histones via exposure to the histone deacetylase inhibitor Trichostatin A during neurogenesis corrects the expression of Notch3 and rescues the development of sensory neurons in embryos lacking the Elp1 Elongator subunit.http://bio.biologists.org/content/10/9/bio058979elongatorelp1h2a.zhistonetsanotch |
| spellingShingle | BreAnna Cameron Elin Lehrmann Tien Chih Joseph Walters Richard Buksch Sara Snyder Joy Goffena Frances Lefcort Kevin G. Becker Lynn George Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway Biology Open elongator elp1 h2a.z histone tsa notch |
| title | Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway |
| title_full | Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway |
| title_fullStr | Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway |
| title_full_unstemmed | Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway |
| title_short | Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway |
| title_sort | loss of elp1 perturbs histone h2a z and the notch signaling pathway |
| topic | elongator elp1 h2a.z histone tsa notch |
| url | http://bio.biologists.org/content/10/9/bio058979 |
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