The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain

The HP1 proteins regulate epigenetic gene silencing by promoting and maintaining chromatin condensation. The HP1 chromodomain binds to methylated histone H3. More enigmatic is the chromoshadow domain (CSD), which mediates dimerization, transcription repression, and interaction with multiple nuclear...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-06, Vol.331 (4), p.929-937
Main Authors: Lechner, Mark S., Schultz, David C., Negorev, Dmitri, Maul, Gerd G., Rauscher, Frank J.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
AFFINITY
Amino Acid Motifs
AMINO ACIDS
ANIMAL CELLS
Animals
Binding Sites
Cell Line
Chromatin
Chromodomain
Chromoshadow domain
Chromosomal Proteins, Non-Histone - chemistry
Chromosomal Proteins, Non-Histone - metabolism
Cornelia de Lange syndrome
DIMERIZATION
DROSOPHILA
Epigenetic
GENE REGULATION
Gene silencing
HETEROCHROMATIN
HP1
Humans
IN VITRO
Mass Spectrometry
MUTANTS
NIPBL
Nuclear Proteins - metabolism
POLYPEPTIDES
Protein Binding
TRANSCRIPTION
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Summary:The HP1 proteins regulate epigenetic gene silencing by promoting and maintaining chromatin condensation. The HP1 chromodomain binds to methylated histone H3. More enigmatic is the chromoshadow domain (CSD), which mediates dimerization, transcription repression, and interaction with multiple nuclear proteins. Here we show that KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid motif, PxVxL, which binds directly to the CSD with high affinity. We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX. Both canonical and variant motifs recognize a similar surface of the CSD dimer as demonstrated by a panel of CSD mutants. These in vitro binding results were confirmed by the analysis of polypeptides found associated with nuclear HP1 complexes and we provide the first evidence of the NIPBL/delangin protein in human cells, a protein recently implicated in the developmental disorder, Cornelia de Lange syndrome. NIPBL is related to Nipped-B, a factor participating in gene activation by remote enhancers in Drosophila melanogaster. Thus, this spectrum of direct binding partners suggests an expanded role for HP1 as factor participating in promoter–enhancer communication, chromatin remodeling/assembly, and sub-nuclear compartmentalization.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.04.016