Rb targets histone H3 methylation and HP1 to promoters

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Rb targets histone H3 methylation and HP1 to
promoters SOREN J. NIELSEN,
ROBERT SCHNEIDER, UTA-MARIA BAUER,
ANDREW J. BANNISTER, ASHBY MORRISON,
DONAL O'CARROLL, RON FIRESTEIN  ,
MICHAEL CLEARY  , THOMAS JENUWEIN,
RAFAEL E. HERRERA TONY KOUZARIDES
 Wellcome/CRC Institute and Department of
Pathology, Tennis Court Road, Cambridge CB2 1QR,
UK Baylor College of Medicine, Department of
Molecular and Cellular Biology, The Breast
Center, 1 Baylor Plaza, Houston, Texas 77030,
USA Research Institute of Molecular Pathology
(IMP), The Vienna Biocenter, Dr. Bohrgasse 7,
A-1030 Vienna, Austria     Department of
Pathology, Stanford University Medical Center,
Stanford, California 94305, USA These authors
have contributed equally to this work.
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INTRODUCTION

• in eukaryote
• SUV39H1 histone methylase
• HP1 methylysine binding protein
• ? functionally interaction ? repress
  transcription
• Lysine 9 of histone H3 is methylated by SUV39H1
• ? creating a binding site for the chromo domain
  of HP1
• we show that SUV39H1 and HP1 are both involved
  in the repressive functions of
• the retinoblastoma (Rb) protein.

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Rb interacts with methylase activity specific for
H3 Lys 9.
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SUV39H1 and Rb interact and regulate
transcription.
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SUV39H1 and Rb interact and regulate
transcription.
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HP1 interacts with Rb in an LXCXE-dependent
fashion.
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Rb is required for HP1 promoter recruitment.
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Rb is required for HP1 promoter recruitment.
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Role of the SUV39H1HP1 complex in the
transcriptional co-repressor function of Rb.
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DISCUSSION

• Methylation by SUV39H1 cannot take place on an
  already acetylated lysine. Thus the deacetylase
  activity associated with Rb may be a necessary
  preceding step to SUV39H1-mediated methylation.
• The precise function of HP1 in repression is
  unclear. HP1 may protect the methyl group on
  Lys 9 from attack from potential demethylases
• HP1 is found associated with a number of
  transcriptional repressors, suggesting that it
  may have a role in repressing many other
  promoters. Thus, the results presented here
  extend the role of SUV39H1 and HP1 beyond
  heterochromatic gene silencing to a more general,
  genome-wide function in repressing gene
  transcription.

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Silencing in heterochromatin, a compact form of
DNA, by the HP1 and SUV39H1 proteins. DNA (blue)
is packaged into nucleosomes by histone proteins
(mauve circles).