Nucleosome Remodeler SNF2L Suppresses Cell Proliferation and Migration and Attenuates Wnt Signaling

Eckey, Maren; Kuphal, Silke; Straub, Tobias; Rümmele, Petra; Kremmer, Elisabeth; Bosserhoff, Anja‐Katrin; Becker, Peter B.

doi:10.1128/mcb.06619-11

Cited by 35 publications

(36 citation statements)

References 56 publications

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“…PCTK3 , cyclin‐dependent kinase 18, also plays a role in the secretory pathway . SMARCA1 encodes an ATPase involved in nucleosome remodeling while RRM2 encodes a subunit of ribonucleotide reductase. We observed that expression of these genes was downregulated in hPSCs seeded at high density as compared to cells seeded at low density (Fig.…”

Section: Resultsmentioning

confidence: 99%

Human pluripotent stem cell culture density modulates YAP signaling

Hsiao

Lampe

Nillasithanukroh

et al. 2016

Biotechnology Journal

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Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs.

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Section: Resultsmentioning

confidence: 99%

Human pluripotent stem cell culture density modulates YAP signaling

Hsiao

Lampe

Nillasithanukroh

et al. 2016

Biotechnology Journal

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“…This would be consistent with our findings of increased TUNEL staining in Snf2h cKO-Nes mice at the onset of GNP expansion. Similarly, RNAi depletion in HeLa or U2OS cells results in increased apoptosis 24 h after SNF2H or ACF1 protein expression was strongly reduced3738. Nonetheless, several alternative explanations exist that could account for the decreased growth of the cerebellum.…”

Section: Discussionmentioning

confidence: 99%

Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation

et al. 2014

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Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h and Snf2l are ATP-dependent chromatin remodelling proteins that assemble, reposition and space nucleosomes, and are robustly expressed in the brain. Here we show that mice conditionally inactivated for Snf2h in neural progenitors have reduced levels of histone H1 and H2A variants that compromise chromatin fluidity and transcriptional programs within the developing cerebellum. Disorganized chromatin limits Purkinje and granule neuron progenitor expansion, resulting in abnormal post-natal foliation, while deregulated transcriptional programs contribute to altered neural maturation, motor dysfunction and death. However, mice survive to young adulthood, in part from Snf2l compensation that restores Engrailed-1 expression. Similarly, Purkinje-specific Snf2h ablation affects chromatin ultrastructure and dendritic arborization, but alters cognitive skills rather than motor control. Our studies reveal that Snf2h controls chromatin organization and histone H1 dynamics for the establishment of gene expression programs underlying cerebellar morphogenesis and neural maturation.

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“…In these follow-up studies, they observed that knockdown of SNF2LT or the full-length SNF2L gene resulted in similar cancer cell-specific phenotypes (Ye et al, 2012). Similar knockdown studies have shown that SNF2L is an essential regulator of the Wnt signaling pathway (Eckey et al, 2012). In these studies, in contradiction to previous SNF2L studies, SNF2L depletion results in increased proliferation and chemotaxis.…”

Section: A Review Of the Literature On Chromatin Remodeling And Camentioning

confidence: 54%

ATP-Dependent Chromatin Remodeling Complexes as Novel Targets for Cancer Therapy

Mayes

Qiu

Alhazmi

et al. 2014

Advances in Cancer Research

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The progression to advanced stage cancer requires changes in many characteristics of a cell. These changes are usually initiated through spontaneous mutation. As a result of these mutations, gene expression is almost invariably altered allowing the cell to acquire tumor-promoting characteristics. These abnormal gene expression patterns are in part enabled by the posttranslational modification and remodeling of nucleosomes in chromatin. These chromatin modifications are established by a functionally diverse family of enzymes including histone and DNA-modifying complexes, histone deposition pathways, and chromatin remodeling complexes. Because the modifications these enzymes deposit are essential for maintaining tumor-promoting gene expression, they have recently attracted much interest as novel therapeutic targets. One class of enzyme that has not generated much interest is the chromatin remodeling complexes. In this review, we will present evidence from the literature that these enzymes have both causal and enabling roles in the transition to advanced stage cancers; as such, they should be seriously considered as high-value therapeutic targets. Previously published strategies for discovering small molecule regulators to these complexes are described. We close with thoughts on future research, the field should perform to further develop this potentially novel class of therapeutic target.

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Nucleosome Remodeler SNF2L Suppresses Cell Proliferation and Migration and Attenuates Wnt Signaling

Cited by 35 publications

References 56 publications

Human pluripotent stem cell culture density modulates YAP signaling

Human pluripotent stem cell culture density modulates YAP signaling

Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation

ATP-Dependent Chromatin Remodeling Complexes as Novel Targets for Cancer Therapy

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