title: TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming.
abstract: Since the discovery of induced pluripotent stem cells there has been intense interest in understanding the mechanisms that allow a somatic cell to be reprogrammed back to a pluripotent state. Several groups have studied the alterations in gene expression that occur as somatic cells modify their genome to that of an embryonic stem cell. Underpinning many of the gene expression changes are modifications to the epigenetic profile of the associated chromatin. We have used a large-scale shRNA screen to identify epigenetic modifiers that act as barriers to reprogramming. We have uncovered an important role for TRIM28 in cells resisting transition between somatic and pluripotent states. TRIM28 achieves this by maintaining the H3K9me3 repressed state and keeping endogenous retroviruses (ERVs) silenced. We propose that knockdown of TRIM28 during reprogramming results in more plastic H3K9me3 domains, dysregulation of genes nearby H3K9me3 marks, and up regulation of ERVs, thus facilitating the transition through reprogramming. Stem Cells 2017;35:147-157.
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Denise Catherine
authors.initials: DC
authors.lastname: Miles
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Nienke Alexandra
authors.initials: NA
authors.lastname: de Vries
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Santiago
authors.initials: S
authors.lastname: Gisler
authors.affiliation: Division of Molecular Carcinogenesis, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Cor
authors.initials: C
authors.lastname: Lieftink
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Waseem
authors.initials: W
authors.lastname: Akhtar
authors.affiliation: Division of Molecular of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gogola
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Inka
authors.initials: I
authors.lastname: Pawlitzky
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Hulsman
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Tanger
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Koppens
authors.affiliation: Division of Molecular Carcinogenesis, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Roderick Leonardus
authors.initials: RL
authors.lastname: Beijersbergen
authors.affiliation: Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.|Cancer Genomics Centre (CGC.nl), Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D065150:Cellular Reprogramming / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000378:metabolism; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008822:Mice, Transgenic; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000076183:Tripartite Motif-Containing Protein 28 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D034741:RNA, Small Interfering; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28; D008239:Lysine
keywords: Epigenetics; Induced pluripotent stem cells; Reprogramming; Trim28