During this work a few new perspectives and ideas for future research developed that could not be pursued due to time constraints. Some of these were mentioned in the discussion and are briefly outlined below:
- Based on the hitherto unknown association of DNMT1 with centromeric heterochromatin in mammalian cells, the results obtained from studies on Drosophila cells should be revisited. DNMT1 associates with some subnuclear structures in about 10% Drosophila cells, which could reflect association with heterochromatin via the TS. This has to be further analyzed by costaining with markers for heterochromatin, like HP1. The TS might bind to some component of heterochromatin that is conserved in Drosophila and mammals.
- The protein component in heterochromatin to which the TS binds has to be identified by 2 hybrid screens or biochemical approaches like affinity purification. It cannot be ruled out that the TS directly binds to DNA at heterochromatin and this has to be tested by studying the ability of the TS to bind to specific DNA sequences from heterochromatic regions.
- The dependence of TS binding to pericentric heterochromatin on other epigenetic modifications such as acetylation and methylation states of histones should be investigated.
- The dynamics of the interaction of DNMT1 with various subnuclear structures at different stages of the cell cycle should be analyzed by fluorescence photobleaching techniques.
- The role of TS mediated retention of DNMT1 in G2 and M phases has to be established.
- The subcellular localization of the DNMT proteins from other organisms like plant and fungi should be analyzed, and the role of the TS in the DNMT1 from these organisms should be elucidated.
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