Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes

Gregory, G. D., Vakoc, C. R., Rozovskaia, T., Zheng, X., Patel, S., Nakamura, T., Canaani, E., Blobel, G. A. (2007) Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Molecular and Cellular Biology, 27 (24). pp. 8466-8479. ISSN 02707306 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17923682
DOI: 10.1128/mcb.00993-07

Abstract

Histone lysine methylation regulates genomic functions, including gene transcription. Previous reports found various degrees of methylation at H3K4, H3K9, and H4K20 within the transcribed region of active mammalian genes. To identify the enzymes responsible for placing these modifications, we examined ASH1L, the mammalian homolog of the Drosophila melanogaster Trithorax group (TrxG) protein Ash1. Drosophila Ash1 has been reported to methylate H3K4, H3K9, and H4K20 at its target sites. Here we demonstrate that mammalian ASHlL associates with the transcribed region of all active genes examined, including Hox genes. The distribution of ASH1L in transcribed chromatin strongly resembles that of methylated H3K4 but not that of H3K9 or H4K20. Accordingly, the SET domain of ASHlL methylates H3K4 in vitro, and knockdown of ASHlL expression reduced H3K4 trimethylation at HoxA10 in vivo. Notably, prior methylation at H3K9 reduced ASH1L-mediated methylation at H3K4, suggesting cross-regulation among these marks. Drosophila ashl and trithorax interact genetically, and the mammalian TrxG protein MLL1 and ASH1L display highly similar distributions and substrate specificities. However, by using MLL null cell lines we found that their recruitments occur independently of each other. Collectively, our data suggest that ASHlL occupies most, if not all, active genes and methylates histone H3 in a nonredundant fashion at a subset of genes. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Item Type: Paper
Uncontrolled Keywords: histone methyltransferase protein ash1l protein derivative protein mll1 unclassified drug animal cell article cell line chromatin controlled study Drosophila melanogaster embryo enzyme localization enzyme specificity gene interaction genetic transcription Hox gene human human cell mammal methylation nonhuman priority journal protein expression Animals Base Sequence DNA-Binding Proteins Gene Expression Regulation Genes, Essential Hela Cells Histone-Lysine N-Methyltransferase Histones Homeodomain Proteins Humans K562 Cells Lysine Mammals Mice Myeloid-Lymphoid Leukemia Protein Protein Binding Protein Structure, Tertiary Transcription Factors Transcription, Genetic Mammalia
Subjects: 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 > protein structure, function, modification > protein methylation > histone methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > methyltransferase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matt Covey
Date: 2007
Date Deposited: 13 Mar 2013 19:39
Last Modified: 13 Mar 2013 19:39
PMCID: PMC2169421
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27797

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