Abstracts (poster) - Wissenschaft Online
Abstracts (poster) - Wissenschaft Online
Abstracts (poster) - Wissenschaft Online
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Bastian Stielow, Alexandra Sapetschnig, Christina Wink, Guntram Suske<br />
SUMO-modified transcription factors repress transcription by<br />
provoking local heterochromatic gene silencing<br />
Following the mechanistic clues provided by our identification of SUMO-dependent<br />
repression components in insect cells (see abstract / <strong>poster</strong> presentation by G. Suske)<br />
we sought to analyze in detail the chromatin changes established by SUMO-modified<br />
transcription factors. We generated a mammalian cell line with a stably integrated<br />
chromatinized Gal4-driven reporter gene that allowed for the readout of the gene<br />
silencing events provoked by SUMOylated transcription factors. Upon transfection,<br />
SUMOylation-competent transcription factors (Gal4 fusions of wildtype Sp3 or<br />
steroidogenic factor 1) repressed transcription whereas the corresponding SUMOylationdeficient<br />
mutants activated transcription of the integrated reporter gene. Chromatinimmunoprecipitations<br />
demonstrate that the promoter-bound SUMO-modified<br />
transcription factors led to the establishment of local repressive chromatin with features<br />
of compacted heterochromatin. SUMO-dependent heterochromatin formation includes<br />
recruitment of the chromatin remodeler Mi-2, the MBT-domain proteins L3MBTL1 and<br />
L3MBTL2, HP1, and the histone methyltransferases SETDB1 and SUV4-20H accompanied<br />
by the establishment of repressive histone modifications such as H3K9 and H4K20<br />
trimethylation. Our results indicate that SUMOylation plays a crucial role in regulating<br />
gene expression by initiating chromatin structure changes that renders DNA inaccessible<br />
to the transcription machinery.<br />
This work was supported by a grant of the DFG to G.S.<br />
Literature<br />
Stielow, B., Sapetschnig, A., Krüger, I., Kunert, N., Brehm, A., Boutros, M. and Suske,<br />
G. (2008). Identification of SUMO-dependent chromatin-associated transcriptional<br />
repression componetnts by a genome-wide RNA interference screen. Mol. Cell, in press.<br />
contact:<br />
Bastian Stielow<br />
Philipps-Universität Marburg<br />
Institut für Molekularbiologie und Tumorforschung<br />
stielow@imt.uni-marburg.de<br />
Emil-Mannkopff-Str. 2<br />
35037 Marburg (Germany)
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