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Published on: January 29, 2018
Modulation of CP2 family transcriptional activity by CRTR-1 and sumoylation
Sarah To1, Stephen J Rodda, Peter D Rathjen
1School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
Abstract:
CRTR-1 is a member of the CP2 family of transcription factors. Unlike other members of the family which are widely expressed, CRTR-1 expression shows specific spatio-temporal regulation. Gene targeting demonstrates that CRTR-1 plays a central role in the maturation and function of the salivary glands and the kidney. CRTR-1 has also recently been identified as a component of the complex transcriptional network that maintains pluripotency in embryonic stem (ES) cells. CRTR-1 was previously shown to be a repressor of transcription. We examine the activity of CRTR-1 in ES and other cells and show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. We also demonstrate that CRTR-1 activity is regulated by sumoylation at a single major site, residue K30. These findings imply that functional redundancy with other family members may mask important roles for CRTR-1 in other tissues, including the blastocyst stage embryo and embryonic stem cells.
Insights
CRTR-1, a transcription factor, is generally an activator, not a repressor, and its activity is regulated by sumoylation. This finding suggests CRTR-1 has important roles in embryonic stem cells and development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- CRTR-1 is a member of the CP2 transcription factor family with specific spatio-temporal expression patterns.
- Previous studies indicated CRTR-1 functions as a transcriptional repressor.
- CRTR-1 is crucial for salivary gland and kidney development and is involved in maintaining embryonic stem cell pluripotency.
Purpose of the Study:
- To investigate the transcriptional activity of CRTR-1 in embryonic stem (ES) cells and other cell types.
- To elucidate the regulatory mechanisms of CRTR-1 activity, including its interaction with other family members.
- To identify post-translational modifications regulating CRTR-1 function.
Main Methods:
- Gene targeting studies to assess CRTR-1 function in vivo.
- In vitro assays to determine CRTR-1's transcriptional activity in various cell lines.
- Analysis of CRTR-1 interactions with CP2, NF2d9, and altNF2d9.
- Site-directed mutagenesis and biochemical assays to study sumoylation at K30.
Main Results:
- CRTR-1 primarily functions as a transcriptional activator, contrary to previous reports.
- CRTR-1 modulates the activity of CP2 family members in a cell-specific manner.
- Sumoylation at residue K30 is a key regulatory mechanism for CRTR-1 activity.
Conclusions:
- CRTR-1's role as a transcriptional activator and its regulation by sumoylation are critical for its function.
- Functional redundancy with other CP2 family members may obscure CRTR-1's specific roles in tissues like the early embryo and ES cells.
- Further research into CRTR-1 is warranted to fully understand its developmental and pluripotency functions.
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