Histone Modifications in Stem Cell Development and Their Clinical Implications

Völker-Albert, Moritz; Bronkhorst, Abel J.; Holdenrieder, Stefan; Imhof, Axel

doi:10.1016/j.stemcr.2020.11.002

Cited by 22 publications

(13 citation statements)

References 77 publications

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“…Recently, studies have been suggested that epigenetic changes such as DNA methylation and histone modifications enhance the events of BCSC metastasis [126][127][128]. miRNAs are epigenetic modulators that target mRNAs without modifying the gene sequences [129,130].…”

Section: Signaling Pathways Induced By Mirnas In Bcscsmentioning

confidence: 99%

Signaling pathways governing breast cancer stem cells behavior

Song¹,

Farzaneh

2021

Stem Cell Res Ther

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Breast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.

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Section: Signaling Pathways Induced By Mirnas In Bcscsmentioning

confidence: 99%

Signaling pathways governing breast cancer stem cells behavior

Song¹,

Farzaneh

2021

Stem Cell Res Ther

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“…Eukaryotic gene expression is regulated by chromatin regulators (CRs) and the histone and DNA modifications they read, write, and remove ( Bannister and Kouzarides, 2011 ; Zhang et al, 2016 ). Chromatin-mediated gene regulation is crucial in development, aging, and disease ( Jambhekar et al, 2019 ; Völker-Albert et al, 2020 ; Zhao and Shilatifard, 2019 ), with classical examples of X-chromosome inactivation and the spatial-temporal control of Hox genes ( Soshnikova and Duboule, 2009 ; Payer, 2017 ). It is also important in synthetic biology, where precise control of gene expression is necessary for probing gene regulatory networks with CRISPRi type screens, for better understanding mechanisms of epigenetic regulation such as cellular reprogramming, and for therapeutic applications such as gene therapy ( Keung et al, 2015 ; Thakore et al, 2016 ; Lienert et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells

Lensch

Herschl

Ludwig

et al. 2022

eLife

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In mammalian cells genes that are in close proximity can be transcriptionally coupled: silencing or activating one gene can affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, and when designing synthetic gene regulation circuits. Here, we systematically dissect this process in single cells by recruiting and releasing repressive chromatin regulators at dual-gene synthetic reporters, and measuring how fast gene silencing and reactivation spread as a function of intergenic distance and configuration of insulator elements. We find that silencing by KRAB, associated with histone methylation, spreads between two genes within hours, with a time delay that increases with distance. This fast KRAB-mediated spreading is not blocked by the classical cHS4 insulators. Silencing by histone deacetylase HDAC4 of the upstream gene can also facilitate background silencing of the downstream gene by PRC2, but with a days-long delay that does not change with distance. This slower silencing can sometimes be stopped by insulators. Gene reactivation of neighboring genes is also coupled, with strong promoters and insulators determining the order of reactivation. Our data can be described by a model of multi-gene regulation that builds upon previous knowledge of heterochromatin spreading, where both gene silencing and gene reactivation can act at a distance, allowing for coordinated dynamics via chromatin regulator recruitment.

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“…Nevertheless, bulk methodologies have been indispensable tools for our current understanding of epigenetics and its relationship with cancer. For example, they allowed for the methylation-based classification of diffuse gliomas (LGm1-LGm6) [135], the potential classification of cancers of unknown primary [123], and the histone modificationbased tracking of cell differentiation states [136].…”

Section: Tumor Heterogeneity and Its Relation To Epigenetic Alterationsmentioning

confidence: 99%