Letter abstract
Nature Cell Biology 10, 489 - 496 (2008)
Published online: 16 March 2008 | doi:10.1038/ncb1713
Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability
Song Shi1, Kimberly Larson1, Dongdong Guo1, Su Jun Lim1, Pranabananda Dutta1, Shian-Jang Yan1 & Willis X. Li1
STAT (Signal transducer and activator of transcription) is a potent transcription factor and its aberrant activation by phosphorylation is associated with human cancers1, 2, 3, 4. We have shown previously that overactivation of JAK, which phosphorylates STAT5, 6, disrupts heterochromatin formation globally in Drosophila melanogaster7. However, it remains unclear how this effect is mediated and whether STAT is involved. Here, we demonstrate that Drosophila STAT (STAT92E) is involved in controlling heterochromatin protein 1 (HP1) distribution and heterochromatin stability. We found, unexpectedly, that loss of STAT92E, had the same effects as overactivation of JAK in disrupting heterochromatin formation and heterochromatic gene silencing, whereas overexpression of STAT92E had the opposite effects. We have further shown that the unphosphorylated or 'transcriptionally inactive' form of STAT92E is localized on heterochromatin in association with HP1, and is required for stabilizing HP1 localization and histone H3 Lys 9 methylation (H3mK9) . However, activation by phosphorylation reduces heterochromatin-associated STAT92E, causing HP1 displacement and heterochromatin destabilization. Thus, reducing levels of unphosphorylated STAT92E, either by loss of STAT92E or increased phosphorylation, causes heterochromatin instability. These results suggest that activation of STAT by phosphorylation controls both access to chromatin and activity of the transcription machinery.
- Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Correspondence to: Willis X. Li1 e-mail: willis_li@urmc.rochester.edu.
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