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Rudolph, T., Yonezawa, M., Lein, S., Heidrich, K., Kubicek, S., Schafer, C., Phalke, S., Walther, M., Schmidt, A., Jenuwin, T., Reuter, G. (2007). Heterochromatin Formation in Drosophila Is Initiated through Active Removal of H3K4 Methylation by the LSD1 Homolog SU(VAR)3-3.  Mol. Cell 26(1): 103--115.
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Epigenetic indexing of chromatin domains by histone lysine methylation requires the balanced coordination of methyltransferase and demethylase activities. Here, we show that SU(VAR)3-3, the Drosophila homolog of the human LSD1 amine oxidase, demethylates H3K4me2 and H3K4me1 and facilitates subsequent H3K9 methylation by SU(VAR)3-9. Su(var)3-3 mutations suppress heterochromatic gene silencing, display elevated levels of H3K4me2, and prevent extension of H3K9me2 at pericentric heterochromatin. SU(VAR)3-3 colocalizes with H3K4me2 in interband regions and is abundant during embryogenesis and in syncytial blastoderm, where it appears concentrated at prospective heterochromatin during cycle 14. In embryos of Su(var)3-3/+ females, H3K4me2 accumulates in primordial germ cells, and the deregulated expansion of H3K4me2 antagonizes heterochromatic H3K9me2 in blastoderm cells. Our data indicate an early developmental function for the SU(VAR)3-3 demethylase in controlling euchromatic and heterochromatic domains and reveal a hierarchy in which SU(VAR)3-3-mediated removal of activating histone marks is a prerequisite for subsequent heterochromatin formation by H3K9 methylation.
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Related Publication(s)
A two-way street: LSD1 regulates chromatin boundary formation in S. pombe and Drosophila.
Chosed and Dent, 2007, Mol. Cell 26(2): 160--162 [FBrf0202005]
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    Mol. Cell
    Molecular Cell
    Publication Year
    1097-2765 1097-4164
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