Journal article
The Role of Med15 Sequence Features in Transcription Factor Interactions
Molecular and cellular biology, Vol.45(2), pp.59-78
02/2025
DOI: 10.1080/10985549.2024.2436672
PMID: 39717019
Abstract
Med15 is a general transcriptional regulator and tail module subunit within the RNA Pol II mediator complex. The
Med15 protein has a well-structured N-terminal KIX domain, three activator binding domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal mediator association domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity using phenotypic, gene expression, transcription factor interaction and phase separation assays of truncation, deletion, and synthetic alleles. We found that individual Med15 activities were influenced by the number of activator binding domains (ABDs) and adjacent polyglutamine tract composition. Robust Med15 activity required at least the Q1 tract and the length of that tract modulated activity in a context-dependent manner. Reduced Msn2-dependent transcriptional activation due to Med15 Q1 tract variation correlated with reduced Msn2:Med15 interaction strength, but interaction strength did not always mirror phase separation propensity. We also observed that distant glutamine tracts and Med15 phosphorylation affected the activities of the KIX domain, and interaction studies revealed that intramolecular interactions may affect some Med15-transcription factor interactions.
Details
- Title: Subtitle
- The Role of Med15 Sequence Features in Transcription Factor Interactions
- Creators
- David G Cooper - Butler UniversityShulin Liu - University of IowaEmma Grunkemeyer - University of IowaJan S Fassler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.45(2), pp.59-78
- DOI
- 10.1080/10985549.2024.2436672
- PMID
- 39717019
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 1098-5549
- eISSN
- 1098-5549
- Publisher
- TAYLOR & FRANCIS INC
- Grant note
- National Science Foundation: RY8740 Nils Johnsson via Addgene
The authors acknowledge the generous gift of strains and plasmids from Dr Patrick Cramer and Mathias Mann, (phospho-site mutant strains), Dr Young Chul Lee (glucocorticoid reporter plasmids), and Nils Johnsson via Addgene (split ubiquitin vectors) and Dr Richard Young for the GFP-Gcn4 expression vector, RY8740. The authors also appreciate comments and suggestions by Dr Daniel Weeks and Dr Bryan Phillips, as well as members of the lab, and anonymous reviewers.
- Language
- English
- Electronic publication date
- 12/24/2024
- Date published
- 02/2025
- Academic Unit
- Biology
- Record Identifier
- 9984759888402771
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