title: Concise Review: Geminin-A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells.
abstract: Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells. In embryonic as well as somatic stem cells, Geminin has been shown to interact with transcription factors and epigenetic regulators to drive gene expression programs and ultimately guide cell fate decisions. An ever-growing number of studies suggests that these interactions of Geminin and proteins regulating transcription are conserved among metazoans. Interactions between Geminin and proteins modifying the epigenome, such as members of the repressive Polycomb group and the SWI/SNF proteins of the permissive Trithorax, have long been established. The complexity of these interactions, however, is only just beginning to unravel, revealing key roles on maintaining stem cell self-renewal and fate specification. In this review, we summarize current knowledge and give new perspectives for the role of Geminin on transcriptional and epigenetic regulation, alongside with its regulatory activity in DNA replication and their implication in the regulation of stem and progenitor cell biology. Stem Cells 2017;35:299-310.
authors.affiliation: Department of Physiology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Patmanidi
authors.affiliation: Department of Physiology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Champeris Tsaniras
authors.affiliation: Department of Physiology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Karamitros
authors.affiliation: Department of Physiology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kyrousi
authors.affiliation: Department of Biology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Lygerou
authors.affiliation: Department of Physiology, Medical School, University of Patras, Rio, Patras, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Taraviras
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000235:genetics*; D044127:Epigenesis, Genetic; D064248:Geminin / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D013234:Stem Cells / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D064248:Geminin
keywords: Cdt1; Chromatin remodeling; DNA replication; Embryonic development; Epigenetic regulation; Geminin; Hematopoietic stem cells; Leukemia; Neural stem cells; Polycomb group; SWitch/Sucrose Non-fermentable; Transcriptional regulation