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Molecular and Cellular Biology, May 2000, p. 3728-3741, Vol. 20, No. 10
Research Institute of Molecular Pathology,
The Vienna Biocenter, A-1030 Vienna, Austria
Received 10 November 1999/Returned for modification 21 December
1999/Accepted 19 February 2000
SUV39H1, a human homologue of the
Drosophila position effect variegation modifier
Su(var)3-9 and of the
Schizosaccharomyces pombe silencing factor
clr4, encodes a novel heterochromatic protein that
transiently accumulates at centromeric positions during mitosis. Using
a detailed structure-function analysis of SUV39H1 mutant proteins in
transfected cells, we now show that deregulated SUV39H1 interferes at
multiple levels with mammalian higher-order chromatin organization.
First, forced expression of full-length SUV39H1 (412 amino acids)
redistributes endogenous M31 (HP1
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Structure-Function Analysis of SUV39H1 Reveals a
Dominant Role in Heterochromatin Organization, Chromosome Segregation,
and Mitotic Progression

and
) and induces abundant associations
with inter- and metaphase chromatin. These properties depend on the
C-terminal SET domain, although the major portion of the SUV39H1
protein (amino acids 89 to 412) does not display affinity for nuclear
chromatin. By contrast, the M31 interaction surface, which was mapped
to the first 44 N-terminal amino acids, together with the immediately
adjacent chromo domain, directs specific accumulation at
heterochromatin. Second, cells overexpressing full-length SUV39H1
display severe defects in mitotic progression and chromosome
segregation. Surprisingly, whereas localization of centromere proteins
is unaltered, the focal, G2-specific distribution of
phosphorylated histone H3 at serine 10 (phosH3) is dispersed in these
cells. This phosH3 shift is not observed with C-terminally truncated
mutant SUV39H1 proteins or with deregulated M31. Together, our data
reveal a dominant role(s) for the SET domain of SUV39H1 in the
distribution of prominent heterochromatic proteins and suggest a
possible link between a chromosomal SU(VAR) protein and histone H3.
*
Corresponding author. Mailing address: Research
Institute of Molecular Pathology, The Vienna Biocenter, Dr. Bohrgasse
7, A-1030 Vienna, Austria. Phone: 43-1-797-30-474. Fax: 43-1-798-7153. E-mail: jenuwein{at}nt.imp.univie.ac.at.
Present address: EMBL, D-69117 Heidelberg, Germany.
Present address: Dairy Science Group, AgResearch, Hamilton, New Zealand.
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