title: LATS2 Positively Regulates Polycomb Repressive Complex 2.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Torigata
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.|DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Okuzaki
authors.initials: O
authors.lastname: Daisuke
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Mukai
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hatanaka
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi, Japan.
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Ohka
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Fukuoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yabuta
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.|DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D057890:Epigenomics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D010766:Phosphorylation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000069896:Transcription Activator-Like Effector Nucleases / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D002843:Chromatin; D006657:Histones; D025521:Tumor Suppressor Proteins; D063151:Polycomb Repressive Complex 2; C092745:LATS1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases; D000069896:Transcription Activator-Like Effector Nucleases