Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1 Journal Article


Authors: Kalakonda, N.; Fischle, W.; Boccuni, P.; Gurvich, N.; Hoya-Arias, R. ; Zhao, X.; Miyata, Y.; Macgrogan, D.; Zhang, J.; Sims, J. K.; Rice, J. C.; Nimer, S. D.
Article Title: Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1
Abstract: Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function. © 2008 Macmillan Publishers Limited All rights reserved.
Keywords: controlled study; protein expression; human cell; methylation; binding affinity; protein function; cell cycle; neoplasm proteins; protein binding; transcription, genetic; mutational analysis; gene expression regulation; amino acid sequence; chromatin; histone-lysine n-methyltransferase; histone h3; tumor protein; binding sites; histones; lysine; protein modification; histone h4; k562 cells; l3mbtl1; lysine monomethylation; pr-set7; protein l3mbtl1
Journal Title: Oncogene
Volume: 27
Issue: 31
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2008-07-17
Start Page: 4293
End Page: 4304
Language: English
DOI: 10.1038/onc.2008.67
PUBMED: 18408754
PROVIDER: scopus
PMCID: PMC2742506
DOI/URL:
Notes: --- - "Cited By (since 1996): 40" - "Export Date: 17 November 2011" - "CODEN: ONCNE" - "Source: Scopus"
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MSK Authors
  1. Jin Zhang
    24 Zhang
  2. Yasuhiko Miyata
    11 Miyata
  3. Piernicola Boccuni
    16 Boccuni
  4. Xiaolan Zhao
    77 Zhao
  5. Stephen D Nimer
    347 Nimer