Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory,Molecular Cell

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Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory
Molecular Cell ( IF 14.5 ) Pub Date : 2024-07-17 , DOI: 10.1016/j.molcel.2024.06.025
Emily R Feierman ₁ , Sean Louzon ₂ , Nicholas A Prescott ₃ , Tracy Biaco ₃ , Qingzeng Gao ₄ , Qi Qiu ₅ , Kyuhyun Choi ₆ , Katherine C Palozola ₇ , Anna J Voss ₁ , Shreya D Mehta ₇ , Camille N Quaye ₇ , Katherine T Lynch ₇ , Marc V Fuccillo ₆ , Hao Wu ₇ , Yael David ₃ , Erica Korb ₇

Affiliation

Neuroscience Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Tri-institutional PhD Program in Chemical Biology, New York, NY, USA.
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

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.

中文翻译：

组蛋白变体 H2BE 增强神经元染色质可及性，促进突触基因表达和长期记忆

组蛋白通过多种机制影响基因表达，包括通过与组蛋白变体的交换。最近的研究结果将组蛋白变异与神经系统疾病联系起来，但很少有在大脑中得到充分研究。最值得注意的是，广泛表达的 H2B 变体仍然难以捉摸。我们应用最近开发的抗体、生化检测和测序方法来揭示 H2B 变体 H2BE 的广泛表达，并确定其在调节染色质结构、神经元转录和小鼠行为中的作用。我们发现 H2BE 在启动子处富集，并且单个独特的氨基酸使其能够显着增强染色质可及性。此外，我们表明 H2BE 对于突触基因表达和长期记忆至关重要。这些数据共同揭示了一种将组蛋白变体与染色质可及性、转录调控、神经元功能和记忆联系起来的机制。这项工作进一步鉴定了广泛表达的 H2B 变体，并揭示了对基因组结构具有深远影响的单个组蛋白氨基酸。

更新日期：2024-07-17

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