LATS2 Positively Regulates Polycomb Repressive Complex 2.

Area of Science:

• Cell Biology
• Epigenetics
• Molecular Biology

Background:

• Large tumor suppressor kinase 2 (LATS2) is a key regulator in the Hippo pathway and influences various cellular processes.
• The precise molecular mechanisms and physiological significance of LATS2's Hippo-independent functions are not fully understood.

Purpose of the Study:

• To elucidate novel functions of LATS2 by investigating its role in regulating epigenetic modifiers.
• To understand the molecular basis of LATS2's involvement in processes beyond the canonical Hippo pathway.

Main Methods:

• Generation of a LATS2 knockout HeLa-S3 cell line using TAL-effector nuclease (TALEN) technology.
• Integrated omics profiling (genomics, transcriptomics, proteomics) of the knockout cell line.
• Cell-cycle analysis and chromatin immunoprecipitation assays.

Main Results:

• LATS2 knockout led to genome-wide downregulation of Polycomb repressive complex 2 (PRC2) and H3K27me3.
• LATS2 directly binds to PRC2 on chromatin and phosphorylates it, enhancing its histone methyltransferase activity.
• LATS2 positively regulates both the expression and activity of PRC2 at mRNA and protein levels.
• PRC2 downregulation in LATS2 knockout cells was independent of cell-cycle aberrations.

Conclusions:

• LATS2 acts as a novel upstream regulator of PRC2, influencing its expression and epigenetic function.
• LATS2 plays a critical role in coordinating the epigenome through direct modulation of PRC2.
• These findings reveal a new layer of epigenetic regulation involving LATS2 and PRC2.