关键词: H2B H2BE chromatin chromatin accessibility epigenetics histone histone variant memory neuron transcription

Mesh : Histones / metabolism genetics Animals Chromatin / metabolism genetics Memory, Long-Term / physiology Neurons / metabolism Mice Synapses / metabolism genetics Promoter Regions, Genetic Mice, Inbred C57BL Gene Expression Regulation Transcription, Genetic Male Humans

来  源:   DOI:10.1016/j.molcel.2024.06.025   PDF(Pubmed)

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.
摘要:
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交换。最近的发现将组蛋白变异与神经系统疾病联系起来,然而,很少有人在大脑中得到很好的研究。最值得注意的是,广泛表达的H2B变体仍然难以捉摸。我们应用了最近开发的抗体,生化化验,和测序方法,以揭示H2B变体H2BE的广泛表达并定义其在调节染色质结构中的作用,神经元转录,和老鼠的行为。我们发现H2BE在启动子处富集,和一个独特的氨基酸使它能够显着增强染色质的可接近性。Further,我们表明H2BE对突触基因表达和长期记忆至关重要。一起,这些数据揭示了一种将组蛋白变体与染色质可及性联系起来的机制,转录调控,神经元功能,和记忆。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。
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