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Comments on Gasser, Susan M. et al. (2013) International Worm Meeting "Heterochromatin organization through development: regulated anchorage by H3K9 methylation and a novel chromodomain protein." (0)
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Gasser, Susan M., Towbin, Benjamin, Gonzalez, Adriana, Zeller, Peter, & Kalck, Veronique (2013). Heterochromatin organization through development: regulated anchorage by H3K9 methylation and a novel chromodomain protein presented in International Worm Meeting. Unpublished information; cite only with author permission.
Heterochromatin comes in several forms and becomes the dominant form of chromatin during terminal differentiation. At least one class of heterochromatin is positioned adjacent to the nuclear lamina. We have created a system in which we can track gene position in developing C. elegans by live fluorescence microscopy. We have found that in differentiated cells, developmentally regulated promoters are at the nuclear periphery when repressed, and shift inwards when active. In early embryonic cells gene positions are not fixed. Using an in vivo model of fluorescently tagged heterochromatin, we have screened for factors that are necessary for anchoring heterochromatin to the nuclear lamina. We find that peripheral anchoring is a direct consequence of sequential methylation reactions by two enzymes that modify histone H3 K9. Mono- and di-methylation of H3K9 mediates anchoring, while silencing of the array requires H3K9 trimethylation. A further screen has identified a novel chromodomain protein that mediates perinuclear anchorage by binding H3K9me, to link chromatin bearing this mark to the nuclear envelope. The physiological effects of disrupting the spatial organization of chromatin through loss of the anchoring machinery will be presented, as well as an RNAi screen for factors that are necessary for survival and differentiation in the absence of heterochromatin, but not in its presence. This reveals fundamental insights into the importance of heterochromatin in development.
Affiliation:
- Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland