Heterochromatin protein 1 (HP1) family members (␣, ␤, and ␥) bind histone H3 methylated at Lys-9, leading to gene silencing and heterochromatin formation. Several previous reports have suggested that HP1s are posttranslationally modified, yet sites of modification have not yet been exhaustively determined. Here we perform the first comprehensive proteomic analysis of all HP1 isoforms using tandem mass spectrometry. Our data reveal that all HP1 isoforms are highly modified in a manner analogous to histones including phosphorylation, acetylation, methylation, and formylation, including several sites having multiple different types of modifications. Additionally, many of these modifications are found in both the chromo-and chromoshadow domains, suggesting that they may have an important role in modulating HP1 interactions or functions. These studies are the first to systematically map the abundant sites of covalent modifications on HP1 isoforms and provide the foundation for future investigations to test whether these modifications are essential in heterochromatin maintenance or other nuclear processes. Molecular & Cellular Proteomics 8: 2432-2442, 2009.The mammalian HP1␣, ␤, and ␥ proteins are a family of chromatin-associated proteins that are homologs of the Drosophila heterochromatin protein 1 (HP1) 1 , originally identified as a protein required for position effect variegation. Position effect variegation is the silencing phenomenon that occurs when a block of euchromatin is placed adjacent to a region of heterochromatin (1). HP1␣, ␤, and ␥ proteins all contain a N-terminal chromodomain (CD) and a C-terminal chromoshadow domain (CSD) that are linked together by a flexible hinge region (2). The CD in HP1 is one of many specialized domains found in a number of other chromatin-associated proteins that recognizes histone post-translational modifications (PTMs). In particular, x-ray crystallographic studies have demonstrated that the HP1 chromodomain binds directly to the histone H3 protein trimethylated on Lys-9 (3).The C-terminal CSD domain is structurally similar to the CD and is thought to be responsible for dimerization and interactions with other proteins. The mammalian HP1␣, ␤, and ␥ proteins have been shown to form both homo-and heterodimers with each other (4). Although the HP1␣, ␤, and ␥ proteins have similar structures and dimerize with each other, studies suggest they have non-overlapping functions. As the name implies, the HP1 proteins are generally associated with constitutive heterochromatic loci; however, HP1␥ localizes with both hetero-and euchromatin (5). Moreover, although microscopy analysis has demonstrated that HP1␣ and HP1␤ localize together at many heterochromatic loci, they do not completely overlap, further suggesting that they can function independently (6). Furthermore, HP1␥ was found to be associated with the DNA of actively transcribed genes by chromatin immunoprecipitation (7).All three of the mammalian HP1 proteins can complex with the co-repressor protein, KAP-1/Tif1␤. Interestingly,...

This review summarizes the treatment and resulting outcomes for total talar dislocation. The PubMed database was searched for articles about humans with total talar dislocation published in the English language in the last twenty years. The following data were entered into a Microsoft Excel spreadsheet: type of dislocation, nature of associated fractures (if any), type of reduction/fixation utilized, immobilization, weight-bearing status, outcome, complications and average follow-up time. Thirty-nine articles reporting a total of 86 cases of total talar dislocation are included in this review. Seventy-three of these were open injuries and 13 closed. Forty-three cases had an associated foot or ankle fracture, 32 of those cases specifically having a fracture of the talus. The talus was preserved in the initial management of 74 cases, whereas the remaining 12 cases were managed by primary talectomy. The mean duration of follow-up was 32 months. Twenty-two cases required a secondary arthrodesis or another additional procedure. A good outcome was achieved in 35% of cases, a fair outcome in 37% and a poor outcome in 27%. The complication of avascular necrosis (AVN) occurred in 22 cases and 14 subjects developed clinically significant osteoarthritis. Generally, the outcome of current treatments associated with total talar dislocation is not ideal, only 1/3 of cases achieving good outcomes. So far, preservation of the talus is the best treatment option. AVN is still a relatively common complication even in the absence of fracture or postoperative infection.

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Level III, retrospective comparative series.

Therapeutic IV.