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Nuclear VANGL2 Inhibits Lactogenic Differentiation.
Biorxiv : the Preprint Server for Biology
|December 18, 2023
Summary
Planar cell polarity protein VANGL2 enters the nucleus and directly binds DNA, regulating mammary cell differentiation. Loss of VANGL2 function promotes differentiation by upregulating STAT5 signaling pathways.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Planar cell polarity (PCP) proteins regulate cell patterning and tissue morphogenesis.
- Intracellular roles of PCP proteins, including transcriptional control, remain largely unknown.
Approach:
- Investigated nuclear localization of the transmembrane PCP protein VANGL2 in HC11 cells, a model for mammary lactogenic differentiation.
- Utilized CUT&RUN assays to identify direct DNA binding of VANGL2 to specific motifs, including the Stat5a promoter.
- Examined the effects of Vangl2 knockdown and overexpression on mammary cell differentiation and gene expression.
Key Points:
- VANGL2 localizes to the nucleus in undifferentiated HC11 cells.
- Loss of Vangl2 function upregulates STAT5 signaling pathways and promotes mammary cell differentiation.
- VANGL2 directly binds to DNA motifs, including the Stat5a promoter, suggesting a transcriptional regulatory role.
Conclusions:
- PCP proteins, like VANGL2, can function intracellularly to regulate gene transcription.
- VANGL2 acts as a transcriptional repressor, keeping differentiation programs in check.
- These findings reveal a novel mechanism by which PCP proteins coordinate tissue morphogenesis through transcriptional control.
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