ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain
Copyright © 2017 Elsevier Ltd. All rights reserved..
The recruitment of transcriptional cofactors by sequence-specific transcription factors challenges the basis of high affinity and selective interactions. Extending previous studies that the N-terminal activation domain (AD) of ETV5 interacts with Mediator subunit 25 (MED25), we establish that similar, aromatic-rich motifs located both in the AD and in the DNA-binding domain (DBD) of the related ETS factor ETV4 interact with MED25. These ETV4 regions bind MED25 independently, display distinct kinetics, and combine to contribute to a high-affinity interaction of full-length ETV4 with MED25. High-affinity interactions with MED25 are specific for the ETV1/4/5 subfamily as other ETS factors display weaker binding. The AD binds to a single site on MED25 and the DBD interacts with three MED25 sites, allowing for simultaneous binding of both domains in full-length ETV4. MED25 also stimulates the in vitro DNA binding activity of ETV4 by relieving autoinhibition. ETV1/4/5 factors are often overexpressed in prostate cancer and genome-wide studies in a prostate cancer cell line indicate that ETV4 and MED25 occupy enhancers that are enriched for ETS-binding sequences and are both functionally important for the transcription of genes regulated by these enhancers. AP1-motifs, which bind JUN and FOS transcription factor families, were observed in MED25-occupied regions and JUN/FOS also contact MED25; FOS strongly binds to the same MED25 site as ETV4 AD and JUN interacts with the other two MED25 sites. In summary, we describe features of the multivalent ETV4- and AP1-MED25 interactions, thereby implicating these factors in the recruitment of MED25 to transcriptional control elements.
| Errataetall: |
CommentIn: J Mol Biol. 2017 Oct 13;429(20):2996-2998. - PMID 28716626 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:429 |
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| Enthalten in: |
Journal of molecular biology - 429(2017), 20 vom: 13. Okt., Seite 2975-2995 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Currie, Simon L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.10.2017 Date Revised 23.01.2023 published: Print-Electronic CommentIn: J Mol Biol. 2017 Oct 13;429(20):2996-2998. - PMID 28716626 Citation Status MEDLINE |
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| doi: |
10.1016/j.jmb.2017.06.024 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM274040387 |
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| 100 | 1 | |a Currie, Simon L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain |
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| 500 | |a CommentIn: J Mol Biol. 2017 Oct 13;429(20):2996-2998. - PMID 28716626 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Ltd. All rights reserved. | ||
| 520 | |a The recruitment of transcriptional cofactors by sequence-specific transcription factors challenges the basis of high affinity and selective interactions. Extending previous studies that the N-terminal activation domain (AD) of ETV5 interacts with Mediator subunit 25 (MED25), we establish that similar, aromatic-rich motifs located both in the AD and in the DNA-binding domain (DBD) of the related ETS factor ETV4 interact with MED25. These ETV4 regions bind MED25 independently, display distinct kinetics, and combine to contribute to a high-affinity interaction of full-length ETV4 with MED25. High-affinity interactions with MED25 are specific for the ETV1/4/5 subfamily as other ETS factors display weaker binding. The AD binds to a single site on MED25 and the DBD interacts with three MED25 sites, allowing for simultaneous binding of both domains in full-length ETV4. MED25 also stimulates the in vitro DNA binding activity of ETV4 by relieving autoinhibition. ETV1/4/5 factors are often overexpressed in prostate cancer and genome-wide studies in a prostate cancer cell line indicate that ETV4 and MED25 occupy enhancers that are enriched for ETS-binding sequences and are both functionally important for the transcription of genes regulated by these enhancers. AP1-motifs, which bind JUN and FOS transcription factor families, were observed in MED25-occupied regions and JUN/FOS also contact MED25; FOS strongly binds to the same MED25 site as ETV4 AD and JUN interacts with the other two MED25 sites. In summary, we describe features of the multivalent ETV4- and AP1-MED25 interactions, thereby implicating these factors in the recruitment of MED25 to transcriptional control elements | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ETS transcription factors | |
| 650 | 4 | |a JUN/FOS. | |
| 650 | 4 | |a Mediator complex. | |
| 650 | 4 | |a Prostate cancer. | |
| 650 | 7 | |a Adenovirus E1A Proteins |2 NLM | |
| 650 | 7 | |a ETV4 protein, human |2 NLM | |
| 650 | 7 | |a MED25 protein, human |2 NLM | |
| 650 | 7 | |a Mediator Complex |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-ets |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-fos |2 NLM | |
| 700 | 1 | |a Doane, Jedediah J |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Kathryn S |e verfasserin |4 aut | |
| 700 | 1 | |a Bhachech, Niraja |e verfasserin |4 aut | |
| 700 | 1 | |a Madison, Bethany J |e verfasserin |4 aut | |
| 700 | 1 | |a Lau, Desmond K W |e verfasserin |4 aut | |
| 700 | 1 | |a McIntosh, Lawrence P |e verfasserin |4 aut | |
| 700 | 1 | |a Skalicky, Jack J |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Kathleen A |e verfasserin |4 aut | |
| 700 | 1 | |a Graves, Barbara J |e verfasserin |4 aut | |
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