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

Lechner, Mark S; Schultz, David C; Negorev, Dmitri; Maul, Gerd G; Rauscher, Frank J

doi:10.1016/j.bbrc.2005.04.016

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

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Abstract

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.

Authors:

Lechner, Mark S ^[1]; Schultz, David C ^[1]; Negorev, Dmitri ^[1]; Maul, Gerd G ^[1]; Rauscher, Frank J ^[1]

Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104 (United States)

Publication Date:: Fri Jun 17 00:00:00 EDT 2005

OSTI Identifier:: 20710791

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 331; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2005.04.016; PII: S0006-291X(05)00776-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; AFFINITY; AMINO ACIDS; ANIMAL CELLS; DIMERIZATION; DROSOPHILA; GENE REGULATION; HETEROCHROMATIN; IN VITRO; MUTANTS; POLYPEPTIDES; TRANSCRIPTION

Citation Formats


                    Lechner, Mark S, Schultz, David C, Negorev, Dmitri, Maul, Gerd G, and Rauscher, Frank J. The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain.  United States: N. p., 2005. 
        Web.  doi:10.1016/j.bbrc.2005.04.016.

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                    Lechner, Mark S, Schultz, David C, Negorev, Dmitri, Maul, Gerd G, & Rauscher, Frank J. The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain.  United States.  https://doi.org/10.1016/j.bbrc.2005.04.016

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                    Lechner, Mark S, Schultz, David C, Negorev, Dmitri, Maul, Gerd G, and Rauscher, Frank J. 2005.  
        "The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain".  United States.  https://doi.org/10.1016/j.bbrc.2005.04.016.

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@article{osti_20710791,

  title        = {The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain},

  author       = {Lechner, Mark S and Schultz, David C and Negorev, Dmitri and Maul, Gerd G and Rauscher, Frank J},

  abstractNote = {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.},

  doi          = {10.1016/j.bbrc.2005.04.016},

  url          = {https://www.osti.gov/biblio/20710791},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 4,

  volume       = 331,

  place        = {United States},

  year         = {Fri Jun 17 00:00:00 EDT 2005},

  month        = {Fri Jun 17 00:00:00 EDT 2005}

}

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