CHMP1 is a novel nuclear matrix protein affecting chromatin structure and cell-cycle progression.
The Polycomb-group (PcG) is a diverse set of proteins required for maintenance of gene silencing during development. In a screen for conserved partners of the PcG protein Polycomblike (Pcl), we have identified a new protein, human CHMP1 (CHromatin Modifying Protein; CHarged Multivesicular body Protein), which is encoded by an alternative open reading frame in the PRSM1 gene and is conserved in both complex and simple eukaryotes. CHMP1 contains a predicted bipartite nuclear localization signal and distributes as distinct forms to the cytoplasm and the nuclear matrix in all cell lines tested. We have constructed a stable HEK293 cell line that inducibly overexpresses CHMP1 under ecdysone control. Overexpressed CHMP1 localizes to a punctate subnuclear pattern, encapsulating regions of nuclease-resistant, condensed chromatin. These novel structures are also frequently surrounded by increased histone H3 phosphorylation and acetylation. CHMP1 can recruit a PcG protein, BMI1, to these regions of condensed chromatin and can cooperate with co-expressed vertebrate Pcl in a Xenopus embryo PcG assay; this is consistent with a role in PcG function. In combination, these observations suggest that CHMP1 plays a role in stable gene silencing within the nucleus.
Stauffer
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Vollum Institute, L474, Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Rd, Portland, OR 97201-3098, USA. stauffer@ohsu.edu
Howard
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Nyun
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Hollenberg
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D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry*; D017124:Conserved Sequence; D056827:Endosomal Sorting Complexes Required for Transport; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D010641:Phenotype; D033921:Vesicular Transport Proteins; D014981:Xenopus / Q000235:genetics
D034961:Antigens, Nuclear; C443709:CHMP1A protein, human; D002843:Chromatin; D056827:Endosomal Sorting Complexes Required for Transport; D009687:Nuclear Proteins; D033921:Vesicular Transport Proteins