title: LIN9, a subunit of the DREAM complex, regulates mitotic gene expression and proliferation of embryonic stem cells.
abstract: The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis.
authors.affiliation: Theodor Boveri Institute, Biocenter, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Esterlechner
authors.forename: Nina
authors.initials: N
authors.lastname: Reichert
authors.forename: Fabian
authors.initials: F
authors.lastname: Iltzsche
authors.forename: Michael
authors.initials: M
authors.lastname: Krause
authors.forename: Florian
authors.initials: F
authors.lastname: Finkernagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Gaubatz
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D011123:Polyploidy; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C512498:LIN-9 protein, mouse; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins; D004247:DNA; D000469:Alkaline Phosphatase