Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory Journal Article
| Authors: | Feierman, E. R.; Louzon, S.; Prescott, N. A.; Biaco, T.; Gao, Q.; Qiu, Q.; Choi, K.; Palozola, K. C.; Voss, A. J.; Mehta, S. D.; Quaye, C. N.; Lynch, K. T.; Fuccillo, M. V.; Wu, H.; David, Y.; Korb, E. |
| Article Title: | Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory |
| Abstract: | Histone proteins affect gene expression through multiple mechanisms, including through exchange with histone variants. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. Most notably, widely expressed variants of H2B remain elusive. We applied recently developed antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters, and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Further, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a mechanism linking histone variants to chromatin accessibility, transcriptional regulation, neuronal function, and memory. This work further identifies a widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure. © 2024 Elsevier Inc. |
| Keywords: | immunohistochemistry; controlled study; promoter region; genetics; nonhuman; polymerase chain reaction; mass spectrometry; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; gene expression; animal experiment; genetic transcription; neurons; transcription, genetic; mice, inbred c57bl; physiology; c57bl mouse; gene expression regulation; brain; messenger rna; epigenetics; histone; chromatin; promoter regions, genetic; western blotting; transcription; plasmid; amino acid; virus infection; memory; fear; histone h2b; neurologic disease; nerve cell culture; nerve cell; amnesia; histones; complementary dna; chromatin structure; synapses; synapse; excitatory postsynaptic potential; brain cell; conditioning; atomic force microscopy; long term memory; habituation; chromatin accessibility; h2b; smelling disorder; humans; human; male; article; memory, long-term; neuron; chromatin immunoprecipitation sequencing; h2be; histone variant; novel object recognition test; open field behavior; t-maze test |
| Journal Title: | Molecular Cell |
| Volume: | 84 |
| Issue: | 15 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2024-08-08 |
| Start Page: | 2822 |
| End Page: | 2837.e11 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2024.06.025 |
| PUBMED: | 39025074 |
| PROVIDER: | scopus |
| PMCID: | PMC11316635 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work