The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
A Specific LSD1/KDM1A Isoform Regulates Neuronal Differentiation through H3K9 Demethylation
Open accessAbstract
Lysine-specific demethylase 1 (LSD1) has been reported to repress and activate transcription by mediating histone H3K4me1/2 and H3K9me1/2 demethylation, respectively. The molecular mechanism that underlies this dual substrate specificity has remained unknown. Here we report that an isoform of LSD1, LSD1+8a, does not have the intrinsic capability to demethylate H3K4me2. Instead, LSD1+8a mediates H3K9me2 demethylation in collaboration with supervillin (SVIL), a new LSD1+8a interacting protein. LSD1+8a knockdown increases H3K9me2, but not H3K4me2, levels at its target promoters and compromises neuronal differentiation. Importantly, SVIL co-localizes to LSD1+8a-bound promoters, and its knockdown mimics the impact of LSD1+8a loss, supporting SVIL as a cofactor for LSD1+8a in neuronal cells. These findings provide insight into mechanisms by which LSD1 mediates H3K9me demethylation and highlight alternative splicing as a means by which LSD1 acquires selective substrate specificities (H3K9 versus H3K4) to differentially control specific gene expression programs in neurons.
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Self-citationLSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription
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DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression
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Cited by
Alternative splicing as a regulator of development and tissue identity
Baralle, F. E., & Giudice, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.27 · Cited by 1,333
Raj, B., & Blencowe, B. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.004 · Cited by 475
Neocortical neurogenesis and the etiology of autism spectrum disorder
Packer, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.002 · Cited by 138
Blazejewski, S. M., Bennison, S. A., Liu, X., & Toyo-oka, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-87521-3 · Cited by 27
Metadata
- Authors
- Laurent, B., Ruitu, L., Murn, J., Hempel, K., Ferrao, R., Xiang, Y., Liu, S., Garcia, B. A., Wu, H., Wu, F., Steen, H., & Shi, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 57
- Issue
- 6
- Pages
- 957-970
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2009089729
- Cited by
- 273
- References
- 41
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Laurent, B., Ruitu, L., Murn, J., Hempel, K., Ferrao, R., Xiang, Y., Liu, S., Garcia, B. A., Wu, H., Wu, F., Steen, H., & Shi, Y. (2015). A Specific LSD1/KDM1A Isoform Regulates Neuronal Differentiation through H3K9 Demethylation. Molecular Cell. https://doi.org/10.1016/j.molcel.2015.01.010
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