Phase separation of YAP-MAML2 differentially regulates the transcriptome Article Swipe
Chan-I Chung
,
Junjiao Yang
,
Xiaoyu Yang
,
Hongjiang Liu
,
Zhimin Ma
,
Frank Szulzewsky
,
Eric C. Holland
,
Yin Shen
,
Xiaokun Shu
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2310430121
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2310430121
Phase separation (PS) drives the formation of biomolecular condensates that are emerging biological structures involved in diverse cellular processes. Recent studies have unveiled PS-induced formation of several transcriptional factor (TF) condensates that are transcriptionally active, but how strongly PS promotes gene activation remains unclear. Here, we show that the oncogenic TF fusion Yes-associated protein 1-Mastermind like transcriptional coactivator 2 (YAP-MAML2) undergoes PS and forms liquid-like condensates that bear the hallmarks of transcriptional activity. Furthermore, we examined the contribution of PS to YAP-MAML2-mediated gene expression by developing a chemogenetic tool that dissolves TF condensates, allowing us to compare phase-separated and non-phase-separated conditions at identical YAP-MAML2 protein levels. We found that a small fraction of YAP-MAML2-regulated genes is further affected by PS, which include the canonical YAP target genes CTGF and CYR61 , and other oncogenes. On the other hand, majority of YAP-MAML2-regulated genes are not affected by PS, highlighting that transcription can be activated effectively by diffuse complexes of TFs with the transcriptional machinery. Our work opens new directions in understanding the role of PS in selective modulation of gene expression, suggesting differential roles of PS in biological processes.
Related Topics
Concepts
Gene
Transcription factor
Transcriptome
Biology
Gene expression
Cell biology
Coactivator
Regulation of gene expression
CTGF
Genetics
Chemistry
Growth factor
Receptor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2310430121
- https://www.pnas.org/doi/pdf/10.1073/pnas.2310430121
- OA Status
- hybrid
- Cited By
- 17
- References
- 76
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391527928
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391527928Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1073/pnas.2310430121Digital Object Identifier
- Title
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Phase separation of YAP-MAML2 differentially regulates the transcriptomeWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-02-05Full publication date if available
- Authors
-
Chan-I Chung, Junjiao Yang, Xiaoyu Yang, Hongjiang Liu, Zhimin Ma, Frank Szulzewsky, Eric C. Holland, Yin Shen, Xiaokun ShuList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2310430121Publisher landing page
- PDF URL
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https://www.pnas.org/doi/pdf/10.1073/pnas.2310430121Direct link to full text PDF
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://www.pnas.org/doi/pdf/10.1073/pnas.2310430121Direct OA link when available
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Gene, Transcription factor, Transcriptome, Biology, Gene expression, Cell biology, Coactivator, Regulation of gene expression, CTGF, Genetics, Chemistry, Growth factor, ReceptorTop concepts (fields/topics) attached by OpenAlex
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17Total citation count in OpenAlex
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2025: 10, 2024: 7Per-year citation counts (last 5 years)
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76Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Yes-associated | 52 |
| abstract_inverted_index.phase-separated | 97 |
| abstract_inverted_index.transcriptional | 27, 56, 71, 161 |
| abstract_inverted_index.transcriptionally | 33 |
| abstract_inverted_index.YAP-MAML2-mediated | 81 |
| abstract_inverted_index.YAP-MAML2-regulated | 113, 140 |
| abstract_inverted_index.non-phase-separated | 99 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 98 |
| corresponding_author_ids | https://openalex.org/A5083537639 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I180670191 |
| citation_normalized_percentile.value | 0.98154725 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |