LSD1 prevents aberrant heterochromatin formation in Neurospora crassa

0537077 - ÚOCHB 2021 RIV GB eng J - Journal Article
Storck, W. K. - Bicocca, V. T. - Rountree, M. R. - Honda, S. - Ormsby, Tereza - Selker, E. U.
LSD1 prevents aberrant heterochromatin formation in Neurospora crassa.
Nucleic Acids Research. Roč. 48, č. 18 (2020), s. 10199-10210. ISSN 0305-1048. E-ISSN 1362-4962
Institutional support: RVO:61388963
Keywords : DNA methylation * histone H3 * facultative heterochromatin
OECD category: Biochemistry and molecular biology
Impact factor: 16.971, year: 2020
Method of publishing: Open access
https://doi.org/10.1093/nar/gkaa724

Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. We explored whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems, orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1. Strains deficient for any of these proteins exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains throughout the genome. Although establishment of H3K9me3 is typically independent of DNA methylation in Neurospora, instances of DNA methylation-dependent H3K9me3 have been found outside regions of canonical heterochromatin. Consistent with this, the hyper-H3K9me3 phenotype of Δlsd1 strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting that spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.
Permanent Link: http://hdl.handle.net/11104/0316284