LATS2 Positively Regulates Polycomb Repressive Complex 2

PLoS One. 2016 Jul 19;11(7):e0158562. doi: 10.1371/journal.pone.0158562. eCollection 2016.


LATS2, a pivotal Ser/Thr kinase of the Hippo pathway, plays important roles in many biological processes. LATS2 also function in Hippo-independent pathway, including mitosis, DNA damage response and epithelial to mesenchymal transition. However, the physiological relevance and molecular basis of these LATS2 functions remain obscure. To understand novel functions of LATS2, we constructed a LATS2 knockout HeLa-S3 cell line using TAL-effector nuclease (TALEN). Integrated omics profiling of this cell line revealed that LATS2 knockout caused genome-wide downregulation of Polycomb repressive complex 2 (PRC2) and H3K27me3. Cell-cycle analysis revealed that downregulation of PRC2 was not due to cell cycle aberrations caused by LATS2 knockout. Not LATS1, a homolog of LATS2, but LATS2 bound PRC2 on chromatin and phosphorylated it. LATS2 positively regulates histone methyltransferase activity of PRC2 and their expression at both the mRNA and protein levels. Our findings reveal a novel signal upstream of PRC2, and provide insight into the crucial role of LATS2 in coordinating the epigenome through regulation of PRC2.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle / genetics
  • Cell Line
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Epigenomics*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Genetic Complementation Test
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • MCF-7 Cells
  • Mice
  • Phosphorylation
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / deficiency
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Transcription Activator-Like Effector Nucleases / genetics
  • Transcription Activator-Like Effector Nucleases / metabolism
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics*


  • Chromatin
  • Histones
  • Tumor Suppressor Proteins
  • Polycomb Repressive Complex 2
  • LATS1 protein, human
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases
  • Transcription Activator-Like Effector Nucleases

Grants and funding

This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Scientific Research B 23370086 [to HN], Scientific Research C 22570185 [to NY], and Research Fellowships for Young Scientists 255951 [to KT]) and by Project MEET, Osaka University Graduate School of Medicine (to DO).