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bioRxiv · 10.1101/2024.11.08.622668

RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination

Galan, C.·Lu, G.·Gill, R.·Li, D.·Liu, Y.·Huh, J. R.·Hang, S.
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Abstract

A gene encoding the transcription factor RTF1 has been associated with an increased risk of ulcerative colitis (UC). In this study, we investigated its function in modulating T cells expressing interleukin-17A (Th17 cells), a cardinal cell type promoting intestinal inflammation. Our results indicate that Rtf1 deficiency disrupts the differentiation of Th17 cells, while leaving regulatory T cells (Treg) unaffected. Mechanistically, RTF1 facilitates histone H2B monoubiquitination (H2Bub1), which requires its histone modification domain (HMD), for supporting Th17 cell function. Impaired Th17 differentiation was also observed in cells lacking the H2Bub1 E3 ligase subunit RNF40, an enzyme known to physically interact with RTF1. Thus, our study underscores the essential role of RTF1 in H2Bub1-mediated epigenetic regulation of Th17 cell differentiation. Understanding this process will likely provide valuable insights into addressing Th17-associated inflammatory disorders. Key PointsO_LIRTF1 is crucial for Th17 cell differentiation via histone H2B monoubiquitination C_LIO_LIRTF1 deficiency impairs Th17 differentiation, similar to H2Bub1 ligase RNF40 deficiency C_LIO_LIRTF1 and H2Bub1 colocalize on genes regulating Th17 cells, indicating an epigenetic role C_LI

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Galan, C., Lu, G., Gill, R., Li, D., Liu, Y., Huh, J. R., Hang, S.. 2024-11-08. RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination. https://doi.org/10.1101/2024.11.08.622668

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