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Gene-specific modulation of TAF10 function by SET9-mediated methylation
Antigone Kouskouti1, Elisabeth Scheer, Adrien Staub
1Institute of Molecular Biology and Biotechnology, FORTH, 711 10 Herakleion, Crete, Greece.
Molecular Cell
|April 22, 2004
Summary
The SET9 enzyme methylates TAF10, enhancing its binding to RNA polymerase II. This modification boosts transcription for specific genes, revealing a novel role for SET9 beyond histone methylation.
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- SET9 is a histone methyltransferase targeting histone 3 at lysine 4.
- While SET9 primarily acts on histones, its non-histone targets and functions are less understood.
- The TBP-associated factor TAF10 is a key component of transcription initiation.
Purpose of the Study:
- To investigate the non-histone targets of SET9.
- To determine the functional consequences of SET9-mediated TAF10 methylation.
- To elucidate the role of TAF10 methylation in gene transcription.
Main Methods:
- In vitro methylation assays to identify SET9 targets.
- Analysis of TAF10-RNA polymerase II interaction.
- Reporter gene assays in TAF10-deficient cells with mutant TAF10.
- Assessment of SET9 recruitment to specific gene promoters.
Main Results:
- SET9 monomethylates TAF10 at a specific lysine residue in its histone-fold domain.
- Methylated TAF10 exhibits increased affinity for RNA polymerase II.
- SET9-mediated TAF10 methylation potentiates transcription of a subset of TAF10-dependent genes.
- Gene-specific effects correlate with SET9 promoter recruitment.
Conclusions:
- SET9 directly methylates TAF10, a non-histone protein.
- TAF10 methylation plays a role in preinitiation complex formation and gene transcription.
- SET9's function extends beyond histones, impacting transcription regulation through TAF10 modification.