Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive

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Methylation of histone H3R2 by PRMT6 and H3K4 by
an MLL complex are mutually exclusive

• Ernesto Guccione, Christian Bassi, Fabio
  Casadio,Francesca Martinato, Matteo Cesaroni,
• Henning Schuchlautz, Bernhard Lu scher Bruno
  Amati

Germany
Italy

Vol 449 18 October 2007 doi10.1038/nature06166
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Levels of chromatin structure
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(No Transcript)
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Chemistry of arginine and lysine methylation
Yi Zhang et al. Genes Dev. 2001 15 2343-2360
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Main theme of this paper
ASH2/WDR5/MLL
PRMT6
1.Arginine methyltransferase PRMT6 catalyses H3R2
di-methylation in vitro And controls global
levels of H3R2me2a in vivo.
H3R2 by PRMT6 H3K4 by
MLL
2.
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Question 1

• To address the distribution of H3R2me2a,
• qChIP (quantitative chromatin immunoprecipitation
  ) on the 110 promoters in P493 cells.

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H3R2me2a is present on inactive promoters, and
within genes independently from the expression
status
TSS
Body
3 end
5 end
Activated promoter
Inactivated promoter
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H3R2me2a is present on inactive promoters, and
within genes independently from the expression
status
5 repressed gene
Inside active gene
Similar pattern As H3K4 me3
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H3R2me2a is present on inactive promoters, and
within genes independently from the expression
status

• H3K4me3 and H3R2me2a are enriched on active and
  inactive promoters, respectively.
• H3R2me2a is found independently of
  transcriptional activity.

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H3R2 methylation by PRMT6
HeLa cells
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H3R2 methylation by PRMT6
Catalytically inactive mutant
293T cells
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H3R2 methylation by PRMT6 is prevented by H3K4me3
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• PRMT6 is an H3R2 methyltransferase, whose ability
  to catalyse the H3R2me2a mark is precluded by
  prior deposition of H3K4me3

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H3R2me2a excludes H3K4 methylationby MLL
complexes
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H3R2me2a excludes H3K4 methylationby MLL
complexes
Pull-down assay
In vitro-translated
U937 nuclear lysates
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H3R2me2a and MLL complex subunits are
counter-correlated on chromatin
Co-occurrence
Counter-correlated
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To the future

• 1. we detected no stable interaction between
  PRMT6 and H3 tail peptides, indicating that
  additional nucleosome domains or proteins might
  be involved.
• 2. to address whether other H3K4-specific
  methyltransferases are insensitive to the
  presence of H3R2me2a.
• 3. In four-cell stage mouse embryos, pluripotent
  blastomeres high levels of H3R2me2aPRMT6 may
  play a role in cell fate determination during
  early embryonic development.

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Thank you