Asymmetric inheritance of epigenetic states in asymmetrically dividing stem cells

Zion, Emily; Chandrasekhara, Chinmayi; Chen, Xin

doi:10.1016/j.ceb.2020.08.003

Cited by 29 publications

(21 citation statements)

References 63 publications

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“…The KEGG analysis revealed that Hypo-HGs were associated with DNA replication, cell cycle, viral carcinogenesis, and spliceosome pathways. During cell division, the precise transmission of epigenetic information to the next generation, such as DNA methylation and histone modification, requires the participation of DNA replication elements to ensure genome stability (18). Abnormal DNA methylation leads to disorders of the DNA replication process, eventually resulting in reduced genomic stability and the occurrence of cancer (19).…”

Section: Discussionmentioning

confidence: 99%

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Cao¹,

Zhang²,

Zhang³

et al. 2022

J Gastrointest Oncol

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Background: Methylation plays an important role in hepatocellular carcinoma (HCC) by altering the expression of key genes. The aim of this study was to screen the aberrantly methylated-differentially expressed genes (DEGs) in HCC and elucidate their underlying molecular mechanism.Methods: Gene expression microarrays (GSE101685) and gene methylation microarrays (GSE44909) were selected. DEGs and differentially methylated genes (DMGs) were screened. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Database for Annotation, Visualization, and Integrated discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyze the functional protein-protein interaction (PPI) network. Molecular Complex Detection (MCODE) analysis was performed using the Cytoscape software. Hub genes were verified in The Cancer Genome Atlas (TCGA) database.Results: A total of 80 hypomethylation-high expression genes (Hypo-HGs) were identified. Pathway enrichment analysis showed DNA replication, cell cycle, viral carcinogenesis, and the spliceosome. The top 5 hub genes were minichromosome maintenance complex component 3 (MCM3), checkpoint kinase 1 (CHEK1), kinesin family member 11 (KIF11), PDZ binding kinase (PBK), and Rac GTPase activating protein 1 (RACGAP1). In addition, 189 hypermethylation-low expression genes (Hyper-LGs) were identified. Pathway enrichment analysis indicated enrichment in metabolic pathways, drug metabolismother enzymes, and chemical carcinogenesis. The top 5 hub genes were leukocyte immunoglobulin like receptor B2 (LILRB2), formyl peptide receptor 1 (FPR1), S100 calcium binding protein A9 (S100A9), S100 calcium binding protein A8 (S100A8), and myeloid cell nuclear differentiation antigen (MNDA). The methylation status and mRNA expression of MCM3, CHEK1, KIF11, PBK, and S100A9 were consistent in the TCGA database and significantly correlated with the prognosis of patients.Conclusions: Combined screening of aberrantly methylated-DEGs based on bioinformatic analysis may provide new clues for elucidating the epigenetic mechanism in HCC. Hub genes, including MCM3, CHEK1, KIF11, PBK, and S100A9, may serve as biomarkers for the precise diagnosis of HCC.

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Section: Discussionmentioning

confidence: 99%

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Cao¹,

Zhang²,

Zhang³

et al. 2022

J Gastrointest Oncol

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“…A monomer is worked 'if ' it is the first one, 'or if' it follows a methylated monomer, 'and if' its 5 th nucleotide is a not yet methylated cytosine ('C'): after recognizing such a monomer, 'readers' are supposed to undergo an allosteric modification: information, likely a satRNA (Bergman et al, 2012), is carried to a control switch of the cell cycle; otherwise, if a methylated ('M') cytosine in the 5 th position silences the current monomer, the processive mechanism is activated and the next monomer is read, interpreted and executed; after processing a monomer, epigenetic complex methylates the 5 th nucleotide, unclasps and disengages from the DNA; so, a bookmarking signal (5mC) updates and keeps track of the counting process. The 5 th nucleotide of the 'start' monomer is used to also state how the cell will divide: 'C' indicates a symmetric division into two 'twin sister' cells; 'H' (5hmC) indicates an asymmetric division (stem cells): the cell will originate one 'unique daughter' differentiating cell: the function 'symm_mitosis' produces a symmetric cell-lineage while the function 'asymm_mitosis' reproduces stem cell divisions (Zion et al, 2020;Elabd et al, 2013). 'A' or 'G' in 4 th or 5 th position in any monomer is not recognized by 'readers': the process fails and stops.…”

Section: The Program 'Mitosis'mentioning

confidence: 99%

Unveiling DNA algorithms: satellite DNA sequences as iterable objects. A computational model.

Regolini¹

2022

Preprint

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Every adult male of the little roundworm Caenorhabditis elegans is always and invariably comprised of exactly 1031 somatic cells, not one more, not one less; and so it is for the adult hermaphrodite (959 somatic cells); its intestine founder cell (the ‘E’ blastomere), if isolated and cultured, undergoes the same number of divisions as in the whole embryo (Robertson et al., 2014); the zygote of Drosophila melanogaster executes 13 cycles of asynchronous cell divisions without cellularization: how are these numbers counted? Artificial Intelligence (First and Second Order Logic, Knowledge graph Engineering) infers that, to perform precise stereotypical numbers of asynchronous cell divisions, a nucleic (genomic) counter is indispensable. Made up of tandemly repeated similar monomers, satellite DNA (satDNA) corresponds to iterable objects used in programming. The purpose of this article is to show how satDNA sequences can be iterated over to count a deterministic number of cell divisions: computational models (attached for free download) are introduced that handle DNA repeated sequences as iterable counters and simulate their use in cells through an epigenetic marker (cytosine methylation) as an iterator. SatDNA, because of its propensity to remodel its structure, can also operate as a strong accelerator in the evolution of complex organs and provides a basis to control interspecific variability of shapes.

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“…These distinct features could be regulated by the differential gene expression in different cell types, which can be extensively regulated by epigenetic mechanisms. Perturbation of proper epigenetic regulation may cause mis-determination of cell fates or cell fate maintenance failure, which can cause cancers, tissue dystrophy, infertility, and ageing [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…In summary, these discoveries in Drosophila male GSCs [ 1 , 3 , 4 ] using this excellent model to study ACD [ 8 , 30–32 ] have established a paradigmatic system to study the molecular and cellular mechanisms of asymmetric epigenetic inheritance. Gaining insights into the spatiotemporal regulation of these phenomena in male GSCs will improve our understanding of how asymmetric histone inheritance is related to distinct cell fate decisions in multicellular organisms.…”

Section: Introductionmentioning

confidence: 99%

Mitotic drive in asymmetric epigenetic inheritance

Ranjan

Chen

2022

Biochemical Society Transactions

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Asymmetric cell division (ACD) produces two daughter cells with distinct cell fates. This division mode is widely used during development and by adult stem cells during tissue homeostasis and regeneration, which can be regulated by both extrinsic cues such as signaling molecules and intrinsic factors such as epigenetic information. While the DNA replication process ensures that the sequences of sister chromatids are identical, how epigenetic information is re-distributed during ACD has remained largely unclear in multicellular organisms. Studies of Drosophila male germline stem cells (GSCs) have revealed that sister chromatids incorporate pre-existing and newly synthesized histones differentially and segregate asymmetrically during ACD. To understand the underlying molecular mechanisms of this phenomenon, two key questions must be answered: first, how and when asymmetric histone information is established; and second, how epigenetically distinct sister chromatids are distinguished and segregated. Here, we discuss recent advances which help our understanding of this interesting and important cell division mode.

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Asymmetric inheritance of epigenetic states in asymmetrically dividing stem cells

Cited by 29 publications

References 63 publications

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Unveiling DNA algorithms: satellite DNA sequences as iterable objects. A computational model.

Mitotic drive in asymmetric epigenetic inheritance

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