ABSTRACT
Post-translational modifications of the N-terminal histone tails, including lysine methylation, have key roles in regulation of chromatin and gene expression. A number of protein modules have been identified that recognize differentially modified histone tails and provide their proteins with the capacity to sense such modifications. Here, we identify the CW domain of plant and animal chromatin-related proteins as a novel module that recognizes different methylated states of lysine 4 on histone H3 (H3K4me). The solution structure of the CW domain of the Arabidopsis ASH1 HOMOLOG2 (ASHH2) histone methyltransferase provides insight into how different CW domains can distinguish different methylated histone tails. We provide evidence that ASHH2 is acting on H3K4me-marked genes, allowing for ASHH2-dependent H3K36 tri-methylation, which contributes to sustained expression of tissue-specific and developmentally regulated genes. This suggests that ASHH2 is a combined 'reader' and 'writer' of the histone code. We propose that different CW domains, dependent on their specificity for different H3K4 methylations, are important for epigenetic memory or participate in switching between permissive and repressive chromatin states.
Subject(s)
Arabidopsis/chemistry , Histone-Lysine N-Methyltransferase/chemistry , Protein Interaction Domains and Motifs , Arabidopsis/metabolism , Gene Expression Profiling , Gene Expression Regulation , Histone Methyltransferases , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Methylation , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Protein Binding , Protein Interaction Mapping , Protein Structure, Tertiary , Surface Plasmon ResonanceABSTRACT
The AMPA type glutamate receptors mediate the majority of fast synaptic transmission in the vertebrate nervous system. Whereas mammals have four subunit genes, Gria1-4, zebrafish has retained a duplicated set of eight genes named gria1-4a and b. We give here a detailed overview of the expression patterns of all eight zebrafish subunits within the developing central nervous system and sensory organs at 24, 48, and 72 hr after fertilization. Expression domains include distinct neuronal subsets in the developing forebrain, midbrain, hindbrain, and spinal cord, as well as in the ganglion- and inner nuclear layers of the retina. As a general rule, each pair of duplicated gria genes is differentially expressed, indicating subfunctionalization of AMPA receptor subunit expression in the teleost lineage. Our findings suggest that zebrafish can serve as a useful model system to investigate the role of AMPA receptors and their differential expression in the vertebrate nervous system.