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Updated: Jan 6, 2026
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
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ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination
Takeshi Tsusaka1, Chikako Shimura1, Yoichi Shinkai1
1Cellular Memory Laboratory, Cluster for Pioneering Research, RIKEN, Wako, Japan.
EMBO Reports
|October 3, 2019
Summary
The nuclear protein ATF7IP regulates the histone methyltransferase SETDB1 by promoting its nuclear localization and increasing its enzymatic activity. This finding sheds light on the regulation of gene silencing pathways.
Area of Science:
- Epigenetics and Gene Regulation
- Molecular Biology
- Biochemistry
Background:
- Histone modification enzymes, like lysine methyltransferases, play crucial roles in gene regulation but their precise control mechanisms are poorly understood.
- SETDB1 (SET domain bifurcated 1) is a key enzyme for H3K9 trimethylation, essential for silencing genes and retrotransposons.
Purpose of the Study:
- To elucidate the regulatory mechanism of SETDB1 enzymatic activity.
- To investigate the role of the nuclear protein ATF7IP in controlling SETDB1 function and localization.
Main Methods:
- Co-immunoprecipitation assays to confirm SETDB1-ATF7IP binding.
- Nuclear export and import assays to track SETDB1 localization.
- Western blotting to assess SETDB1 ubiquitination and activity levels.
Main Results:
- ATF7IP binds to the N-terminal region of SETDB1, inhibiting its nuclear export and promoting nuclear import.
- Nuclear localization of SETDB1 leads to increased ubiquitination and enhanced enzymatic activity.
- ATF7IP acts as a crucial regulator for SETDB1's nuclear translocation and subsequent activation.
Conclusions:
- ATF7IP is a key regulator of SETDB1, controlling its nuclear localization and thereby modulating its histone methyltransferase activity.
- This mechanism provides insight into the regulation of H3K9 trimethylation and its role in gene silencing.
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