title: The dosage of Patz1 modulates reprogramming process.
abstract: The acquisition of pluripotent cells can be achieved by combined overexpression of transcription factors Oct4, Klf4, Sox2 and c-Myc in somatic cells. This cellular reprogramming process overcomes various barriers to re-activate pluripotency genes and re-acquire the highly dynamic pluripotent chromatin status. Many genetic and epigenetic factors are essentially involved in the reprogramming process. We previously reported that Patz1 is required for maintenance of ES cell identity. Here we report that Patz1 plays an inhibitory role in OKSM-induced reprogramming process since more iPS colonies can be induced from Patz1(+/-) MEFs than wild type MEFs; while the addition of Patz1 significantly repressed reprogramming efficiency. Patz1(+/-) MEFs can surpass the senescence barrier of Ink4a/Arf locus, thus enhancing iPS colonies formation. Moreover, Patz1(+/-) MEFs displayed higher levels of acetylated histone H3, H3K4me2, H3K4me3, H3K36me3 and lower levels of histone H3K9me3 and HP1α, indicating that heterozygous knockout of Patz1 results in a globally open chromatin which is more accessible for transcriptional activation. However, Patz1(-/-) MEFs gave the lowest reprogramming efficiency which may result from cell senescence trigged by up-regulated Ink4a/Arf locus. Together, we have demonstrated that the dosage of Patz1 modulates reprogramming process via significantly influencing cell senescence, proliferation and chromatin structure.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD6, Centre for Translational Medicine, Level 14, South Core, 14 Medical Drive Singapore 117597.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD6, Centre for Translational Medicine, Level 14, South Core, 14 Medical Drive Singapore 117597.
authors.forename: Jin Rong
authors.initials: JR
authors.lastname: Ow
authors.affiliation: Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672.
authors.forename: Bobby Cheng Peow
authors.initials: BC
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD6, Centre for Translational Medicine, Level 14, South Core, 14 Medical Drive Singapore 117597.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Goh
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Lo Kwee-Seong Integrated Biomedical Sciences Building, Shatin, NT, Hong Kong.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.
authors.forename: Yuin Han
authors.initials: YH
authors.lastname: Loh
authors.affiliation: Institute of Experimental Endocrinology and Oncology, CNR, 80131 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
authors.affiliation: Center for Individualized Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD6, Centre for Translational Medicine, Level 14, South Core, 14 Medical Drive Singapore 117597.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics* / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D002843:Chromatin / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006657:Histones / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D002843:Chromatin; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006657:Histones; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors