Fig. 7: Hoxc8 interacts with P-TEFb to promote the transcriptional elongation of fibrotic genes. | Nature Communications

Fig. 7: Hoxc8 interacts with P-TEFb to promote the transcriptional elongation of fibrotic genes.

From: Methionine restriction alleviates kidney fibrosis through epigenetic repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis

Fig. 7: Hoxc8 interacts with P-TEFb to promote the transcriptional elongation of fibrotic genes.

A Co-immunoprecipitation (Co-IP) analysis showing the interaction between FLAG-CDK9 and HA-HOXC8 in 293 T cells. B Co-IP analysis showing the interaction between MYC-CDK9 and FLAG-HOXC8 in 293 T cells. C Co-IP analysis of endogenous Hoxc8, Cdk9, and CycT1 in NRK-49F cells treated with or without TGF-β. D Composite plots showing normalized Hoxc8 ChIP-seq signals across gene bodies (3 kb ± ChIP-seq peak summit) in control, TGF-β-treated, and TGF-β+siHoxc8-treated NRK-49F cells. E Composite plots showing Pol II Ser2P ChIP-seq signals across gene bodies (3 kb ± ChIP-seq peak summit) in control, TGF-β-treated, and TGF-β+siHoxc8-treated NRK-49F cells. F Cumulative distribution plot of Pol II pausing index (PI) for genes overlapped between MetR- and siHoxc8-suppressed gene sets. G Working model of the regulation of Hoxc8 and pro-fibrotic gene expression under TGF-β and MetR treatments. Top panel (red dashed box): TGF-β induces Hoxc8 expression through Smad3 activation. Once upregulated, Hoxc8 undergoes self-activation and interacts with P-TEFb to promote transcriptional elongation of pro-fibrotic genes. Bottom panel (blue dashed box): MetR suppresses TGF-β-induced myofibroblast activation by inhibiting Hoxc8 expression. This disrupts P-TEFb recruitment, thereby reducing transcriptional elongation of pro-fibrotic genes. Independent experiments = 3. Source data are provided as a Source Data file.

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