ETS2

Cilia effects upon perturbation of ETS2

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (z=2.61) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Ciliopathy associations

• STAR Syndrome

Subcellular localization

cilia associated gene, cytosol, nucleoplasm, plasma membrane

Functional category

• Motile cilium & axoneme; Ciliary assembly/disassembly

Function

We identify a transcriptional repression mechanism involving Preferentially Expressed Antigen in Melanoma (PRAME) and the transcription factor ETS2 as key modulators of ciliogenesis. We demonstrate an inverse correlation between PRAME expression and primary cilia formation in melanoma cells (R = −0.83, p = 0.042), and show that PRAME knockdown significantly promotes ciliogenesis, underscoring its role as a negative regulator. Integrative analyses combining our RNA-seq data with publicly available ChIP-seq data (GSE26439) and promoter motif analysis revealed that both PRAME and ETS2 are recruited to shared promoter regions of intraflagellar transport (IFT) genes, which are essential for cilia assembly. Notably, PRAME specifically interacts with ETS2, but not ETS1, indicating a selective and functionally relevant interaction. Similar to PRAME, ETS2 overexpression suppresses ciliogenesis and downregulates IFT gene expression. Mechanistically, the PRAME-ETS2 complex recruits histone deacetylase 1 (HDAC1) to IFT gene promoters, leading to epigenetic silencing via histone deacetylation(PMID: 41700497).