Chromodomain-Mediated Oligomerization of HP1 Suggests a Nucleosome-Bridging Mechanism for Heterochromatin Assembly

• Published in: Molecular cell Vol. 41; no. 1; pp. 67 - 81
• Main Authors: Canzio, Daniele, Chang, Evelyn Y., Shankar, Smita, Kuchenbecker, Kristopher M., Simon, Matthew D., Madhani, Hiten D., Narlikar, Geeta J., Al-Sady, Bassem
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.01.2011
• Subjects: Chromatin; Chromatin Assembly and Disassembly; Chromosomal Proteins, Non-Histone - metabolism; Chromosomal Proteins, Non-Histone - physiology; heterochromatin; Heterochromatin - metabolism; histones; Histones - metabolism; Methylation; nucleosomes; Nucleosomes - metabolism; peptides; Protein Multimerization; Schizosaccharomyces pombe Proteins - metabolism; Schizosaccharomyces pombe Proteins - physiology; Substrate Specificity
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2010.12.016

HP1 proteins are central to the assembly and spread of heterochromatin containing histone H3K9 methylation. The chromodomain (CD) of HP1 proteins specifically recognizes the methyl mark on H3 peptides, but the same extent of specificity is not observed within chromatin. The chromoshadow domain of HP1 proteins promotes homodimerization, but this alone cannot explain heterochromatin spread. Using the S. pombe HP1 protein, Swi6, we show that recognition of H3K9-methylated chromatin in vitro relies on an interface between two CDs. This interaction causes Swi6 to tetramerize on a nucleosome, generating two vacant CD sticky ends. On nucleosomal arrays, methyl mark recognition is highly sensitive to internucleosomal distance, suggesting that the CD sticky ends bridge nearby methylated nucleosomes. Strengthening the CD-CD interaction enhances silencing and heterochromatin spread in vivo. Our findings suggest that recognition of methylated nucleosomes and HP1 spread on chromatin are structurally coupled and imply that methylation and nucleosome arrangement synergistically regulate HP1 function. [Display omitted] ► Recognition of nucleosomal H3K9me3 mark is coupled to Swi6 tetramerization via CD ► Recognition of the methyl mark is sensitive to internucleosomal distance ► Strengthening CD-CD interaction enhances silencing in vivo