Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression

Area of Science:

• Molecular Biology
• Cancer Research
• Gene Regulation

Background:

• Anillin (ANLN) is a known mitotic protein and oncoprotein, but its nuclear functions remain largely uncharacterized.
• Understanding ANLN's role in the nucleus is crucial for elucidating its oncogenic mechanisms.

Purpose of the Study:

• To investigate the function of nuclear anillin (ANLN) in gene transcriptional regulation within cancer cells.
• To explore the ANLN-RNA polymerase II (Pol II) interaction and its impact on transcriptional activity.

Main Methods:

• Investigated nuclear ANLN's interaction with RNA polymerase II (Pol II) large subunit.
• Observed ANLN-Pol II complex formation and transcriptional condensate dynamics.
• Utilized short-term ANLN depletion to assess effects on Pol II chromatin binding and enhancer activity.
• Examined the impact of THZ1, a super-enhancer inhibitor, on ANLN-Pol II clustering and cancer cell proliferation.

Main Results:

• Nuclear ANLN directly interacts with the RNA polymerase II (Pol II) large subunit, forming transcriptional condensates.
• ANLN enhances Pol II clustering and promotes Pol II CTD phase separation, influencing chromatin binding and enhancer-mediated transcription.
• Target genes regulated by the ANLN-Pol II axis are implicated in oxidoreductase activity, Wnt signaling, and cell differentiation.
• THZ1 specifically inhibits ANLN-Pol II clustering, downstream gene expression, and esophageal squamous cell carcinoma (ESCC) cell proliferation.

Conclusions:

• Nuclear ANLN plays a significant role in gene transcriptional regulation by modulating RNA polymerase II (Pol II) activity.
• The ANLN-Pol II axis is critical for the proliferation of esophageal squamous cell carcinoma (ESCC) cells.
• Targeting the ANLN-Pol II interaction with inhibitors like THZ1 presents a potential therapeutic strategy for ESCC.