Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin

Li, F., Huarte, M., Zaratiegui, M., Vaughn, M. W., Shi, Y., Martienssen, R., Cande, W. Z. (October 2008) Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin. Cell, 135 (2). pp. 272-83. ISSN 1097-4172 (Electronic)0092-8674 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/18957202
DOI: 10.1016/j.cell.2008.08.036

Abstract

In most eukaryotes, histone methylation patterns regulate chromatin architecture and function: methylation of histone H3 lysine-9 (H3K9) demarcates heterochromatin, whereas H3K4 methylation demarcates euchromatin. We show here that the S. pombe JmjC-domain protein Lid2 is a trimethyl H3K4 demethylase responsible for H3K4 hypomethylation in heterochromatin. Lid2 interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, which also functions in the RNA interference pathway. Disruption of the JmjC domain alone results in severe heterochromatin defects and depletion of siRNA, whereas overexpressing Lid2 enhances heterochromatin silencing. The physical and functional link between H3K4 demethylation and H3K9 methylation suggests that the two reactions act in a coordinated manner. Surprisingly, crossregulation of H3K4 and H3K9 methylation in euchromatin also requires Lid2. We suggest that Lid2 enzymatic activity in euchromatin is regulated through a dynamic interplay with other histone-modification enzymes. Our findings provide mechanistic insight into the coordination of H3K4 and H3K9 methylation.

Item Type: Paper
Uncontrolled Keywords: Chromosome Segregation DNA-Binding Protein metabolism Euchromatin metabolism Heterochromatin metabolism Histone-Lysine N-Methyltransferase Histones chemistry metabolism Lysine metabolism Models Biological Oxidoreductases N-Demethylating chemistry metabolism Point Mutation Protein Methyltransferases metabolism Protein Structure Tertiary RNA Interference Schizosaccharomyces chemistry genetics metabolism Schizosaccharomyces pombe Proteins chemistry metabolism Transcription Factors metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation > histone methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation
CSHL Authors:
Communities: CSHL labs > Martienssen lab
Depositing User: Matt Covey
Date: 17 October 2008
Date Deposited: 26 Feb 2013 16:59
Last Modified: 26 Feb 2013 16:59
PMCID: PMC2614271
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27559

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