SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes
The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus h...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89493 |
| _version_ | 1797456730244775936 |
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| author | Baira Godneeva Maria Ninova Katalin Fejes-Toth Alexei Aravin |
| author_facet | Baira Godneeva Maria Ninova Katalin Fejes-Toth Alexei Aravin |
| author_sort | Baira Godneeva |
| collection | DOAJ |
| description | The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus’s repressive activity. SUMOylation influences Bonus’s subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2–10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression. |
| first_indexed | 2024-03-09T16:11:02Z |
| format | Article |
| id | doaj.art-75cb819e59cc4b4f84accdf5463bbe71 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-09T16:11:02Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | eLife |
| spelling | doaj.art-75cb819e59cc4b4f84accdf5463bbe712023-11-24T16:11:35ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.89493SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genesBaira Godneeva0https://orcid.org/0009-0004-1662-8844Maria Ninova1Katalin Fejes-Toth2Alexei Aravin3https://orcid.org/0000-0002-6956-8257California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United States; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian FederationUniversity of California, Riverside, Riverside, United StatesCalifornia Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United StatesCalifornia Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United StatesThe conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus’s repressive activity. SUMOylation influences Bonus’s subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2–10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression.https://elifesciences.org/articles/89493heterochromatinSUMOtranscriptional regulationgerm cells |
| spellingShingle | Baira Godneeva Maria Ninova Katalin Fejes-Toth Alexei Aravin SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes eLife heterochromatin SUMO transcriptional regulation germ cells |
| title | SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes |
| title_full | SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes |
| title_fullStr | SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes |
| title_full_unstemmed | SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes |
| title_short | SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes |
| title_sort | sumoylation of bonus the drosophila homolog of transcription intermediary factor 1 safeguards germline identity by recruiting repressive chromatin complexes to silence tissue specific genes |
| topic | heterochromatin SUMO transcriptional regulation germ cells |
| url | https://elifesciences.org/articles/89493 |
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