Journal
GENE
Volume 397, Issue 1-2, Pages 161-168Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2007.04.027
Keywords
epigenetic regulation; historic lysine methyltransferase; chromatin structure; SET domain
Categories
Funding
- MRC [MC_U117512796] Funding Source: UKRI
- Medical Research Council [MC_U117512796] Funding Source: researchfish
- Medical Research Council [MC_U117512796] Funding Source: Medline
Ask authors/readers for more resources
Drosophila discs absent, small, or homeotic-1 (ASH1) is a member of trithorax-group proteins that play essential roles in epigenetic regulation of Hex genes. Drosophila ASH I genetically interacts with trithorax and has been reported to methylate historic H3 lysine 4 (K4) as well as H3 K9 and H4 K20. The function of mammalian ASH I, by contrast, has remained largely unknown. Here we report a historic lysine scanning mutation assay using recombinant core histories and in vitro reconstituted nucleosomes to identify targets of mammalian methyltransferases by fluorographic, Western blot, and mass spectrometric analyses. The assay reproduced specificities of previously known histone methyltransferases and further revealed unexpectedly that mammalian ASH1 mono- or di-methylates histone H3 K36 but not any other lysine residues of recombinant unmodified mammalian histories. Under the same experimental condition, lysine to arginine substitution of histone H3 at position 36 abolished the methyltransferase activity of Drosophila ASH1, suggesting that K36 is their specific target. We also demonstrate that native ASH1 proteins, consisting of the carboxy-tenninal domains including the catalytic site, retain the specificity for K36. Taken together, our data suggest that ASH1 subfamily of SET domain proteins have K36-specific methyltransferase activities evolutionarily conserved from flies to mammals. (C) 2007 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available