@article{d77f673c49fc4c13b0fc06bf97957ee4,
title = "LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control",
abstract = "We found that a neuron-specific isoform of LSD1, LSD1n, which results from an alternative splicing event, acquires a new substrate specificity, targeting histone H4 Lys20 methylation, both in vitro and in vivo. Selective genetic ablation of LSD1n led to deficits in spatial learning and memory, revealing the functional importance of LSD1n in neuronal activity-regulated transcription that is necessary for long-term memory formation. LSD1n occupied neuronal gene enhancers, promoters and transcribed coding regions, and was required for transcription initiation and elongation steps in response to neuronal activity, indicating the crucial role of H4K20 methylation in coordinating gene transcription with neuronal function. Our results indicate that this alternative splicing of LSD1 in neurons, which was associated with altered substrate specificity, serves as a mechanism acquired by neurons to achieve more precise control of gene expression in the complex processes underlying learning and memory.",
author = "Jianxun Wang and Francesca Telese and Yuliang Tan and Wenbo Li and Chunyu Jin and Xin He and Harihar Basnet and Qi Ma and Daria Merkurjev and Xiaoyan Zhu and Zhijie Liu and Jie Zhang and Kenny Ohgi and Havilah Taylor and White, {Ryan R.} and Cagdas Tazearslan and Yousin Suh and Macfarlan, {Todd S.} and Pfaff, {Samuel L.} and Rosenfeld, {Michael G.}",
note = "Funding Information: We thank J. Chen (University of California San Diego, UCSD) for pLNL vector for LSD1n gene targeting, and S. Wu and M. Capecchi (University of Utah) for pCAG-LSL vector for generation of Lsd1 transgenic mice. We thank J. Zhao and E. Kothari (UCSD transgenic core) for generating knockout and transgenic mice, S. Roberts (The Scripps Research Institute Mouse Behavioral Core) for behavioral assessment, H. Karten (UCSD) for brain anatomy analysis, M. Ghassemian (UCSD) for MALDI-TOF mass spectrometry analysis, A. Gamliel, R. McEvilly, I. Garcia-Bassets, B. Bloodgood and C.K. Glass (UCSD) for discussion, comments, suggestions and critical reading of the manuscript, R. Pardee for proofreading of the manuscript, and J. Hightower for help with figure preparation. J.W. receives funding from a US National Institutes of Health T32 Postdoctoral Fellowship. F.T. was supported by grants from the Roche Extending Innovation Network Program. W.L. was supported by a Department of Defense postdoctoral fellowship. S.L.P. (Benjamin H. Lewis Chair in Neuroscience) and M.G.R. receive funding from the Howard Hughes Medical Institute. This research was supported by grants from the National Institute of Neurological Disorders and Stroke (R37NS5037116) to S.L.P. and by grants from the US National Institutes of Health and the National Cancer Institute (DK018477, NS034934, DK039949, HL065445 and CA173903) to M.G.R. Y.S. received funding from the US National Institutes of Health and the National Institute of General Medical Sciences (R01GM104459-01).",
year = "2015",
month = aug,
day = "26",
doi = "10.1038/nn.4069",
language = "English (US)",
volume = "18",
pages = "1256--1264",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "9",
}