Context-Dependent Requirement of Euchromatic Histone Methyltransferase Activity during Reprogramming to Pluripotency

Vidal, Simon E.; Polyzos, Alexander; Chatterjee, Kaushiki; Ee, Ly-Sha; Swanzey, Emily; Morales-Valencia, Jorge; Wang, Hongsu; Parikh, Chaitanya N.; Amlani, Bhishma; Tu, Shengjiang; Gong, Yixiao; Snetkova, Valentina; Skok, Jane A.; Tsirigos, Aristotelis; Kim, Sang Yong; Apostolou, Effie; Stadtfeld, Matthias

doi:10.1016/j.stemcr.2020.08.011

Cited by 7 publications

(4 citation statements)

References 63 publications

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“…A recent study showed that overexpression of the RAS oncogene in wild type mouse embryonic fibroblasts (MEFs) enhanced their dedifferentiation, but transformation of the same cells by deleting p53 or Arf tumor suppressors precluded it ( Ferreirós et al, 2019 ). Similar interactions and context dependency were observed for histone marks as well ( Nagaraja et al, 2019 ; Vidal et al, 2020 ). These data indicate that cancer cells diverge into distinct epigenetic programs, and likely change their cellular context, at the early stages of transformation.…”

Section: Pervasive Uncertainty In Targeting Cellular Componentssupporting

confidence: 75%

Targeting the Transcriptome Through Globally Acting Components

et al. 2021

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Transcription is a step in gene expression that defines the identity of cells and its dysregulation is associated with diseases. With advancing technologies revealing molecular underpinnings of the cell with ever-higher precision, our ability to view the transcriptomes may have surpassed our knowledge of the principles behind their organization. The human RNA polymerase II (Pol II) machinery comprises thousands of components that, in conjunction with epigenetic and other mechanisms, drive specialized programs of development, differentiation, and responses to the environment. Parts of these programs are repurposed in oncogenic transformation. Targeting of cancers is commonly done by inhibiting general or broadly acting components of the cellular machinery. The critical unanswered question is how globally acting or general factors exert cell type specific effects on transcription. One solution, which is discussed here, may be among the events that take place at genes during early Pol II transcription elongation. This essay turns the spotlight on the well-known phenomenon of promoter-proximal Pol II pausing as a step that separates signals that establish pausing genome-wide from those that release the paused Pol II into the gene. Concepts generated in this rapidly developing field will enhance our understanding of basic principles behind transcriptome organization and hopefully translate into better therapies at the bedside.

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Section: Pervasive Uncertainty In Targeting Cellular Componentssupporting

confidence: 75%

Targeting the Transcriptome Through Globally Acting Components

et al. 2021

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“…Frontiers in Cell and Developmental Biology frontiersin.org reprogramming efficiency (Wang et al, 2011;Vidal et al, 2020). Onder et al showed that H3K79 dimethylation (H3K79me2) prevented repression of lineage-specific programs and acted as a barrier during reprogramming.…”

Section: Histone Changes During Reprogrammingmentioning

confidence: 99%

“…As an epigenetic mark that is mainly associated with gene repression, H3K9 methylation acts as a major obstacle to reprogramming. Induction of certain histone demethylases or using siRNAs against H3K9 methyltransferases has been found to enhance reprogramming efficiency ( Wang et al, 2011 ; Vidal et al, 2020 ). Onder et al showed that H3K79 dimethylation (H3K79me2) prevented repression of lineage-specific programs and acted as a barrier during reprogramming.…”

Section: Reprogramming and The Associated Epigenetic Changesmentioning

confidence: 99%

Induced pluripotent stem cells: Generation methods and a new perspective in COVID-19 research

Karami

Moradi

Eidi

et al. 2023

Front. Cell Dev. Biol.

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Induced pluripotent stem cells (iPSCs) exhibit an unlimited ability to self-renew and produce various differentiated cell types, thereby creating high hopes for both scientists and patients as a great tool for basic research as well as for regenerative medicine purposes. The availability and safety of iPSCs for therapeutic purposes require safe and highly efficient methods for production of these cells. Different methods have been used to produce iPSCs, each of which has advantages and disadvantages. Studying these methods would be very helpful in developing an easy, safe, and efficient method for the generation of iPSCs. Since iPSCs can be generated from somatic cells, they can be considered as valuable cellular resources available for important research needs and various therapeutic purposes. Coronavirus disease 2019 (COVID-19) is a disease that has endangered numerous human lives worldwide and currently has no definitive cure. Therefore, researchers have been rigorously studying and examining all aspects of COVID-19 and potential treatment modalities and various drugs in order to enable the treatment, control, and prevention of COVID-19. iPSCs have become one of the most attractive and promising tools in this field by providing the ability to study COVID-19 and the effectiveness of drugs on this disease outside the human body. In this study, we discuss the different methods of generation of iPSCs as well as their respective advantages and disadvantages. We also present recent applications of iPSCs in the study and treatment of COVID-19.

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“…While these antibodies were chosen for their widespread use in many publications [39][40][41][42][43], we considered that the antibodies themselves may lack specificity; however, we found that the antibodies were indeed specific when histone peptides were displayed in a different context. Specifically, when the same set of peptides was linked to the surface of yeast (instead of magnetic beads) through the display of modified monovalent streptavidin (mSA) [44][45][46] (Figure 3c), the same antibodies were able to specifically bind to their target epitope and showed significantly less binding to nontarget epitopes (Figure 3b, right).…”

Section: Antibodies Label More Specifically When Histone Peptides Are Presented On Yeast Versus Bead Surfacesmentioning

confidence: 99%

Modified Histone Peptides Linked to Magnetic Beads Reduce Binding Specificity

Meanor

Keung

Rao

2022

IJMS

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Histone post-translational modifications are small chemical changes to the histone protein structure that have cascading effects on diverse cellular functions. Detecting histone modifications and characterizing their binding partners are critical steps in understanding chromatin biochemistry and have been accessed using common reagents such as antibodies, recombinant assays, and FRET-based systems. High-throughput platforms could accelerate work in this field, and also could be used to engineer de novo histone affinity reagents; yet, published studies on their use with histones have been noticeably sparse. Here, we describe specific experimental conditions that affect binding specificities of post-translationally modified histones in classic protein engineering platforms and likely explain the relative difficulty with histone targets in these platforms. We also show that manipulating avidity of binding interactions may improve specificity of binding.

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Context-Dependent Requirement of Euchromatic Histone Methyltransferase Activity during Reprogramming to Pluripotency

Cited by 7 publications

References 63 publications

Targeting the Transcriptome Through Globally Acting Components

Targeting the Transcriptome Through Globally Acting Components

Induced pluripotent stem cells: Generation methods and a new perspective in COVID-19 research

Modified Histone Peptides Linked to Magnetic Beads Reduce Binding Specificity

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