c-Jun as a one-way valve at the naive to primed interface DOI Creative Commons
Dongwei Li,

Ling Luo,

Lin Guo

и другие.

Cell & Bioscience, Год журнала: 2023, Номер 13(1)

Опубликована: Окт. 14, 2023

c-Jun is a proto-oncogene functioning as transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role early embryonic development remains unknown. Here, we show that acts one-way valve preserve the primed state impair reversion naïve state. induced during naive transition, it works stabilize chromatin structure inhibit reverse transition. Loss of has surprisingly little effect on no phenotypic cells, however, cells loss leads failure correctly close naïve-specific enhancers. When are reprogram state, these enhancers more rapidly activated when lost or impaired, conversion efficient. The results this study indicate can function stabilizer EpiSCs, maintain epigenetic cell type act for fate conversions.

Язык: Английский

Insights into the Histone Acetylation-Mediated Regulation of the Transcription Factor Genes That Control the Embryogenic Transition in the Somatic Cells of Arabidopsis DOI Creative Commons
Joanna Morończyk, Agnieszka Brąszewska-Zalewska, Barbara Wójcikowska

и другие.

Cells, Год журнала: 2022, Номер 11(5), С. 863 - 863

Опубликована: Март 2, 2022

Somatic embryogenesis (SE), which is a process that involves the in vitro-induced embryogenic reprogramming of plant somatic cells, requires dynamic changes cell transcriptome. These are fine-tuned by many genetic and epigenetic factors, including posttranslational histone modifications such as acetylation. Antagonistically acting enzymes, acetyltransferases (HATs) deacetylases (HDACs), control acetylation developmental processes, believed to SE. However, function specific HAT/HDACs genes subjected acetylation-mediated regulation during SE have yet be revealed. Here, we present global gene-specific Arabidopsis explants undergoing In TSA (trichostatin A)-induced SE, demonstrate H3 H4 might expression critical transcription factor (TF) vital role LEC1, LEC2 (LEAFY COTYLEDON 1; 2), FUS3 (FUSCA 3) MYB118 (MYB DOMAIN PROTEIN 118). Within HATs HDACs, mainly positively regulate identified HDA19 negatively affecting regulating BBM. Finally, provide some evidence on Our results reveal an essential mechanisms TF play roles cells. The implicate complexity Hac-related gene induction point differences regulatory involved auxin- TSA-induced

Язык: Английский

Процитировано

20
Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state DOI Creative Commons
Yang Yang, Liyang Shi,

Xiuling Fu

и другие.

PLoS Biology, Год журнала: 2022, Номер 20(6), С. e3001682 - e3001682

Опубликована: Июнь 30, 2022

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this are unclear. Here, we show that arrested enter senescent-like state, marked by cell cycle arrest, down-regulation ribosomes and histones MYC p53 activity. can be divided into 3 types. Type I fail complete maternal-zygotic transition, II/III have low levels glycolysis either high (Type II) or III) oxidative phosphorylation. Treatment with SIRT agonist resveratrol nicotinamide riboside (NR) partially rescue phenotype, which is accompanied changes metabolic Overall, our data suggests epigenetic dysfunctions underlie embryos.

Язык: Английский

Процитировано

20
MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia DOI Creative Commons
Ali Afgar,

Sattarzadeh Bardsiri Mahla,

Reza Vahidi

и другие.

eJHaem, Год журнала: 2024, Номер 5(1), С. 191 - 205

Опубликована: Фев. 1, 2024

Abstract Small noncoding ribonucleic acids called microRNAs coordinate numerous critical physiological and biological processes such as cell division, proliferation, death. These regulatory molecules interfere with the function of many genes by binding 3'‐UTR region target mRNAs to inhibit their translation or even degrade them. Given that a large proportion miRNAs behave either tumor suppressors oncogenes, any genetic epigenetic aberration changeing structure and/or could initiate formation development. An example cancers is chronic lymphocytic leukemia (CLL), most prevalent adult in Western nations, which caused unregulated growth buildup defective cells peripheral blood lymphoid organs. Genetic alterations at cellular molecular levels play an important role occurrence development CLL. In this vein, it was noted disease noticeably affected changes expression miRNAs. Many studies on have shown these are pivotal prognosis different cancers, including CLL, (e.g., methylation) can predict progression response treatment. Furthermore, involved drug resistance targeting be considered new therapeutic approach for treatment disease. MiRNA screening offer information etiology Considering importance gene regulation, application diagnosis, prognosis, CLL reviewed paper.

Язык: Английский

Процитировано

3
Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies DOI Creative Commons
Wooli Bae,

Eun A.,

Myon‐Hee Lee

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 3, 2025

Pluripotent stem cells (PSCs) possess the extraordinary capability to differentiate into a variety of cell types. This is tightly regulated by epigenetic mechanisms, particularly histone modifications. Moreover, reprogramming somatic or fate-committed induced pluripotent (iPSCs) largely relies on these modifications, such as methylation and acetylation histones. While extensive research has been conducted utilizing mouse models, significance modifications in human iPSCs gaining increasing recognition. Recent studies underscore importance regulators both process regulation cancer (CSCs), which are pivotal tumor initiation development treatment resistance. review elucidates dynamic alterations that impact emphasizes necessity for balance between activating repressive marks. These marks influenced enzymes DNA methyltransferases (DNMTs) deacetylases (HDACs). Furthermore, this explores therapeutic strategies aimed at targeting enhance efficacy while advancing understanding pluripotency reprogramming. Despite promising developments creation inhibitors histone-modifying enzymes, challenges selectivity therapy resistance continue pose significant hurdles. Therefore, future endeavors must prioritize biomarker-driven approaches gene-editing technologies optimize therapies.

Язык: Английский

Процитировано

0
A specific pluripotency-associated eRNA controls Nanog locus by shaping the epigenetic landscape and stabilizing enhancer–promoter interaction DOI Creative Commons
Mariella Cuomo, Davide Costabile, Rosa Della Monica

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(7)

Опубликована: Март 31, 2025

Despite a plethora of studies exploring the transcriptional regulation Nanog gene, role enhancer RNAs (eRNAs) derived from Nanog-interacting super-enhancers (SEs) remains under-investigated. In present study, we examined functional eRNAs transcribed -5 kb SE in mouse embryonic stem cells (mESCs) and found that an eRNA, here defined as -5KNAR, was essential to maintain locus epigenetically active configuration, thereby ensuring pluripotency. We identified -5KNAR functionally interacts with RAD21 protein, suggesting stabilizing cohesin complex at locus, generation maintenance enhancer-promoter loop. Silencing caused cascade events, including DNA methylation wave (likely spreading single methylated CpG site), substantial chromatin remodeling, loss loop, inducing silencing mESC differentiation. Under these conditions, exogenous re-expression unable restore either endogenous expression or interaction, that, hierarchical level, plays prominent maintaining pluripotency mESCs.

Язык: Английский

Процитировано

0
Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression DOI Creative Commons
Tianzhe Zhang, Ran Zheng, Li Mao

и другие.

Nucleic Acids Research, Год журнала: 2022, Номер 50(9), С. 4959 - 4973

Опубликована: Апрель 14, 2022

Human endogenous retroviruses, also called LTR elements, can be bound by transcription factors and marked different histone modifications in biological contexts. Recently, individual or certain subclasses of LTRs such as LTR7/HERVH LTR5_Hs/HERVK families have been identified cis-regulatory elements. However, there are still many elements with unknown functions. Here, we dissected the landscape regulatory map integrating 98 ChIP-seq data human embryonic stem cells (ESCs), annotated active enriching enhancer/promoter-related marks. Notably, found that MER57E3 functionally acted proximal element to activate respective ZNF gene. Additionally, HERVK transcript could mainly function nucleus adjacent genes. Since LTR5_Hs/LTR5 was early embryo-specific factors, further investigated expression dynamics pluripotent states. LTR5_Hs/LTR5/HERVK exhibited higher level naïve ESCs extended (EPSCs). Functionally, high activity serve a distal enhancer regulate host Ultimately, our study not only provides comprehensive ESCs, but explores models genome.

Язык: Английский

Процитировано

13
A programmable system to methylate and demethylate N6-methyladenosine (m6A) on specific RNA transcripts in mammalian cells DOI Creative Commons
Chen Chang, Gang Ma, Edwin Cheung

и другие.

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(11), С. 102525 - 102525

Опубликована: Сен. 23, 2022

RNA N6-methyladenosine (m6A) is the most abundant internal mRNA modification and forms part of an epitranscriptomic system that modulates function. m6A reversibly catalyzed by specific enzymes, those modifications can be recognized RNA-binding proteins in turn regulate biological processes. Although there are many reports demonstrating participation critical functions, this exploration has mainly been conducted through global KO or knockdown writers, erasers, readers m6A. Consequently, a lack information about role on single transcripts processes, posing challenge understanding functions Here, we demonstrate CRISPR/dCas13a-based editors, which target RNAs using multiple CRISPR array to methylate demethylate human 293T cells mouse embryonic stem cells. We systematically assay its capabilities enable targeted rewriting dynamics, including modulation circular translation transcript half-life. Finally, use specifically modulate levels noncoding XIST (X-inactive transcript) X chromosome silencing activation. The editors described here used explore roles

Язык: Английский

Процитировано

11
ATRX guards against aberrant differentiation in mesenchymal progenitor cells DOI Creative Commons
Fang Yan, Douglas Barrows,

Yakshi Dabas

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 52(9), С. 4950 - 4968

Опубликована: Март 13, 2024

Abstract Alterations in the tumor suppressor ATRX are recurrently observed mesenchymal neoplasms. has multiple epigenetic functions including heterochromatin formation and maintenance regulation of transcription through modulation chromatin accessibility. Here, we show murine progenitor cells (MPCs) that Atrx deficiency aberrantly activated differentiation programs. This includes adipogenic pathways where loss induced expression factors enhanced response to stimuli. These changes linked near lineage genes together with increased accessibility gains active marks. We additionally depletion H3K9me3 at transposable elements, which derepressed they could serve as regulatory elements. Finally, demonstrated a malignancy, undifferentiated pleomorphic sarcoma, results similar disruption de-repression Together, our reveal role for maintaining states transcriptional repression progenitors preventing aberrant context.

Язык: Английский

Процитировано

2
Hydrogels mimicking the viscoelasticity of extracellular matrix for regenerative medicine: Design, application, and molecular mechanism DOI
Lichen Li, Shuhan Wang, You‐Tzung Chen

и другие.

Chemical Engineering Journal, Год журнала: 2024, Номер 498, С. 155206 - 155206

Опубликована: Авг. 28, 2024

Язык: Английский

Процитировано

2
DUX: One Transcription Factor Controls 2-Cell-like Fate DOI Open Access
Wei Ren, Leilei Gao,

Yaling Mou

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(4), С. 2067 - 2067

Опубликована: Фев. 13, 2022

The double homeobox (Dux) gene, encoding a transcription factor, is one of the key drivers totipotency in mice. Recent studies showed Dux was temporally expressed at 2-cell stage and acted as transcriptional activator during zygotic genome activation (ZGA) embryos. A similar occurs mouse embryonic stem cells, giving rise to 2-cell-like cells (2CLCs). Though molecular mechanism underlying this expanded 2CLC potency caused by has been partially revealed, regulation mechanisms controlling expression remain elusive. Here, we discuss latest advancements multiple levels expression, well function 2CLCs transition, aiming provide theoretical framework for understanding that regulate totipotency.

Язык: Английский

Процитировано

10