(Dub) 9 : There Are Various Reasons Behind It (...
(Dub) 9 : There Are Various Reasons Behind It (... >>> https://geags.com/2tlaOB
Impact of H3K27me3 on H2Aub deposition: An initial model involved PRC2 recruitment at PcG target genes and recognition of H3K27me3 by Pc through its trimethyl-lysine binding domain known as chromodomain49,53,70,71,72,73. While this implied that PRC2 and PRC1 are sequentially recruited to the same regions to deposit H3K27me3 and subsequently H2Aub, respectively, many studies provided evidence for different mechanisms of H2Aub deposition53,54,55. First, as mentioned above, in Drosophila, PRC1 can be directly recruited to chromatin through PhoRC55. Second, mutation of Drosophila E(z), which strongly reduces H3K27me3, had only a minimal effect on the global levels of H2Aub26. Interestingly, while a significant reduction of H2Aub was observed around PREs following inactivation of PRC2, only a marginal decrease of global H2Aub levels was observed74. In mammals, several studies indicated that the bulk of genomic H2Aub does not depend on PRC2 and H3K27me345,75,76,77,78. For example, in mESC which lacks the PRC2 component EED, global H2Aub levels remain unchanged in the absence of H3K27me345,75. Moreover, it was found that deposition of H2Aub on inactivated X chromosome is independent of PRC2 and precedes H3K27me3 deposition79,80. However, other studies in mESC and somatic cells showed that inactivation of PRC2 can result in significantly decreased levels H2Aub both globally and on gene regulatory regions81,82. The reasons behind these discrepancies are unclear, but are likely to be associated with variations in cell systems and experimental conditions used. Thus, while a possible general model seems to point toward H2Aub being largely independent of H3K27me3, definitive answers on the role of H3K27 methylation in shaping H2A ubiquitination are still needed. 59ce067264