S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription

Lan, Fei, Zaratiegui, Mikel, Villen, Judit, Vaughn, Matthew W., Verdel, Andre, Huarte, Maite, Shi, Yujiang, Gygi, Steven P., Moazed, Danesh, Martienssen, Robert A., Shi, Yang (2007) S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription. Mol Cell, 26 (1). pp. 89-8101. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/17434129
DOI: 10.1016/j.molcel.2007.02.023

Abstract

LSD1 represses and activates transcription by demethylating histone H3K4me and H3K9me, respectively. Genetic ablation of the S. pombe homologs, splsd1 and splsd2, resulted in slow growth and lethality, respectively, underscoring their physiological importance. spLsd1 and spLsd2 form a stable protein complex, which exhibits demethylase activity toward methylated H3K9 in vitro. Both proteins were associated with the heterochromatin boundary regions and euchromatic gene promoters. Loss of spLsd1 resulted in increased H3K9 methylation accompanied by reduced euchromatic gene transcription and heterochromatin propagation. Removal of the H3K9 methylase Clr4 partially suppressed the slow growth phenotype of splsd1Delta. Conversely, catalytically inactivating point mutations in the splsd1 and splsd2 genes partially mimicked the growth and heterochromatin propagation phenotypes. Taken together, these findings suggest the importance of both enzymatic and nonenzymatic roles of spLsd1 in regulating heterochromatin propagation and euchromatic transcription and also suggest that misregulation of spLsd1/2 is likely to impact the epigenetic state of the cell.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Cell Survival DNA Methylation Euchromatin Gene Expression Regulation, Fungal Genome, Fungal Heterochromatin Histones Molecular Sequence Data Oxidoreductases, N-Demethylating Schizosaccharomyces Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Transcription, Genetic
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics > heterochromatin
CSHL Authors:
Communities: CSHL labs > Martienssen lab
Depositing User: Matt Covey
Date Deposited: 06 Jan 2014 21:40
Last Modified: 06 Jan 2014 21:40
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29199

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