Chromodomains in a variety of proteins mediate the formation of heterochromatin by interacting directly with histone H3, DNA, or RNA. A diverse family of long terminal repeat (LTR)-retrotransposons possesses chromodomains in their integrases (IN), suggesting that the chromodomains may control integration. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is highly active and possesses a chromodomain in the COOH terminus of its IN. To test this chromodomain for a role in integration, recombinant INs with and without the chromodomain were assayed for activity in in vitro reactions. The full-length IN had integration activity with oligonucleotide substrates that modeled both the insertion reaction and a reverse reaction known as disintegration. The INs of retroviruses possess an additional activity termed 3' processing that must remove 2-3 nucleotides from the 3' ends of the viral cDNA before insertion can occur. These additional nucleotides are added during reverse transcription because of the position of the minus strand primer downstream of the LTR. The position of the primer for Tf1 suggests no nucleotides are added 3' of the LTR. It was therefore surprising that Tf1 IN was capable of 3' cleavage. The most unexpected result reported here was that the IN lacking the chromodomain had significantly higher activity and substantially reduced substrate specificity. These results reveal that both the activity and specificity of enzymes can be modulated by their chromodomains.
"The transposition activity of the MAGGY retrotransposon of the rice blast fungus Magnaporthe oryzae dramatically decreased with the loss or alteration of the chromodomain . On the other hand, the chromointegrase of the Tf1 LTR retrotransposon from Schizosaccharomyces pombe that lacks the chromodomain demonstrated a significantly higher activity and a substantially reduced substrate specificity . As was demonstrated recently, the MAGGY chromodomain interacts with H3K9me2 and H3K9me3 in a similar way compared to the HP1 " classical " chromodomain. "
[Show abstract][Hide abstract] ABSTRACT: Chromodomain-containing LTR retrotransposons are one of the most successful groups of mobile elements in plant genomes. Previously, we demonstrated that two types of chromodomains (CHDs) are carried by plant LTR retrotransposons. Chromodomains from group I (CHD_I) were detected only in Tcn1-like LTR retrotransposons from nonseed plants such as mosses (including the model moss species Physcomitrella) and lycophytes (the Selaginella species). LTR retrotransposon chromodomains from group II (CHD_II) have been described from a wide range of higher plants. In the present study, we performed computer-based mining of plant LTR retrotransposon CHDs from diverse plants with an emphasis on spike-moss Selaginella. Our extended comparative and phylogenetic analysis demonstrated that two types of CHDs are present only in the Selaginella genome, which puts this species in a unique position among plants. It appears that a transition from CHD_I to CHD_II and further diversification occurred in the evolutionary history of plant LTR retrotransposons at approximately 400 MYA and most probably was associated with the evolution of chromatin organization.
International Journal of Plant Genomics 04/2012; 2012(21):874743. DOI:10.1155/2012/874743
"However, HIV-1 IN has been reported to bind to several chromatin-associated proteins (Kalpana et al. 1994; Peytavi et al. 1999). Furthermore, a family of related integrase enzymes encoded by yeast retrotransposons contains chromodomains which bind methylated histone tails (Hizi and Levin 2005). In addition, cellular proteins recruited by specific histone modifications may contribute to integration. "
[Show abstract][Hide abstract] ABSTRACT: Drugs of abuse serve as cofactors to susceptibility to HIV infection and disease progression. Although clinical reports indicate association between HIV/AIDS and drug use, the molecular mechanism of infection susceptibility and disease progression remains unclear. Drugs such as cocaine exert their addictive effects in part by epigenetic mechanisms. Given that epigenetic modifications play an important role in HIV-1 life cycle, it is essential to unravel whether drug abuse-associated epigenetic changes may contribute to HIV/AIDS. In this article we will provide a prospective on the impact of epigenetic mechanisms on HIV-1 life cycle.
Life sciences 10/2010; 88(21-22):995-9. DOI:10.1016/j.lfs.2010.10.005 · 2.70 Impact Factor
"However, it remains to be determined whether endogenous small RNAs (such as piRNAs that silence retrotransposons) elicit transcriptional gene silencing in mammals. It is important to note that several retrotransposons are targeted to integrate within regions of heterochromatin by a chromodomain motif within the integrase protein (Kordis 2005; Hizi et al. 2005; Gao et al. 2008). It has recently been demonstrated in flies that Piwi, which binds piRNAs to mediate transposon silencing, interacts directly with the chromodomain protein HP1a (Brower-Toland et al. 2007), and that this interaction is required for transcriptional gene silencing. "
[Show abstract][Hide abstract] ABSTRACT: In fission yeast, assembly of centromeric heterochromatin requires the RITS complex, which consists of Ago1, Tas3, Chp1, and siRNAs derived from centromeric repeats. Recruitment of RITS to centromeres has been proposed to depend on siRNA-dependent targeting of Ago1 to centromeric sequences. Previously, we demonstrated that methylated lysine 9 of histone H3 (H3K9me) acts upstream of siRNAs during heterochromatin establishment. Our crystal structure of Chp1's chromodomain in complex with a trimethylated lysine 9 H3 peptide reveals extensive sites of contact that contribute to Chp1's high-affinity binding. We found that this high-affinity binding is critical for the efficient establishment of centromeric heterochromatin, but preassembled heterochromatin can be maintained when Chp1's affinity for H3K9me is greatly reduced.
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