epigenetic factor
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2021 ◽  
Author(s):  
Weifang Wu ◽  
Toni McHugh ◽  
David A Kelly ◽  
Alison L Pidoux ◽  
Robin C Allshire

The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-ACnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-ACnp1 overexpression bypasses heterochromatin dependency, suggesting heterochromatin ensures exposure to conditions or locations permissive for CENP-ACnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-ACnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-ACnp1 chromatin assembly occurs when central domain DNA is placed near, but not far from, endogenous centromeres or neocentromeres. Moreover, direct tethering of central domain DNA at SPBs permits CENP-ACnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation because target sequences are exposed to high levels of CENP-ACnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.


Author(s):  
Lingyue Li ◽  
Yiyu Wang ◽  
Yuan Mou ◽  
Hao Wu ◽  
Ye Qin

Background. Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available. Methods. We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0. Results. KDM1A was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis. Conclusions. Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.


2021 ◽  
Vol 36 (1) ◽  
Author(s):  
Lei Liu ◽  
Ting‐Ting Liu ◽  
Guo‐Guang Xie ◽  
Xiao‐Qi Zhu ◽  
Yun Wang

2021 ◽  
pp. 106896
Author(s):  
Bárbara Guerra-Carvalho ◽  
David F. Carrageta ◽  
Luís Crisóstomo ◽  
Rui A. Carvalho ◽  
Marco G. Alves ◽  
...  

2021 ◽  
Vol 2 ◽  
Author(s):  
Xiao Han ◽  
Zhipeng Fan

Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cell with the potential of self-renewal and multidirectional differentiation. They can be obtained from a variety of tissues and can differentiate into a variety of cell types under different induction conditions, including osteoblasts. Because of this osteogenic property, MSCs have attracted much attention in the treatment of bone metabolism-related diseases. MicroRNAs (miRNAs), as an epigenetic factor, are thought to play an important regulatory role in the process of osteogenic differentiation of MSCs. In recent years, increasingly evidence shows that miRNAs imbalance is involved in the regulation of osteoporosis and fracture. In this review, miRNAs involved in osteogenic differentiation and their mechanisms for regulating the expression of target genes are reviewed. In addition, we also discuss the potential clinical applications and possible directions of this field in the future.


2021 ◽  
Vol 7 (32) ◽  
pp. eabf3898
Author(s):  
Di Sun ◽  
Yanjun Li ◽  
Zeyang Ma ◽  
Xingxing Yan ◽  
Niankui Li ◽  
...  

Posttranscriptional gene silencing (PTGS) is a regulatory mechanism to suppress undesired transcripts. Here, we identified Flowering locus VE (FVE), a well-known epigenetic component, as a new player in cytoplasmic PTGS. Loss-of-function fve mutations substantially reduced the accumulation of transgene-derived small interfering RNAs (siRNAs). FVE interacts with suppressor of gene silencing 3 (SGS3), a master component in PTGS. FVE promotes SGS3 homodimerization that is essential for its function. FVE can bind to single-stranded RNA and double-stranded RNA (dsRNA) with moderate affinities, while its truncated form FVE-8 has a significantly increased binding affinity to dsRNA. These affinities affect the association and channeling of SGS3-RNA to downstream dsRNA binding protein 4 (DRB4)/Dicer-like protein 2/4 (DCL2/4) complexes. Hence, FVE, but not FVE-8, biochemically enhances the DRB4/DCL2/4 activity in vitro. We surmise that FVE promotes production of transgene-derived siRNAs through concertedly tuning SGS3-DRB4/DCL2/4 functions. Thus, this study revealed a noncanonical role of FVE in PTGS.


2021 ◽  
Author(s):  
Adrián Salas-Bastos ◽  
Martin Treppner ◽  
Josip S. Herman ◽  
Dimitrios Koutsogiannis ◽  
Harald Binder ◽  
...  

Despite conceptual research on hippocampus development and the application of single-cell-resolved technologies, the nature and maturation of its diverse progenitor populations are unexplored. The chromatin modifier DOT1L balances progenitor proliferation and differentiation, and conditional loss-of-function mice featured impaired hippocampus development. We applied single-cell RNA sequencing on DOT1L-mutant mice and explored cell trajectories in the E16.5 hippocampus. We resolved in our data five distinct neural stem cell populations with the developmental repertoire to specifically generate the cornu ammonis (CA) 1 field and the dentate gyrus (DG). Within the two developing CA1- and CA3-fields, we identified two distinct maturation states and we thus propose CA1- and CA3-differentiation along the radial axis. In the developing hippocampus, DOT1L is primarily involved in the proper development of CA3 and the DG, and it serves as a state-preserving epigenetic factor that orchestrates the expression of several important transcription factors that impact neuronal differentiation and maturation.


2021 ◽  
Author(s):  
Imane Saif ◽  
Amal Bouziyane ◽  
Mustapha Benhessou ◽  
Mohamed El karroumi ◽  
Moulay Mustapha Ennaji

Abstract Background: The promoter region is a key element of gene expression regulation. In mammals, most of the genes present, at the level of their promoter, a large number of islands CpG. Age is seen as another factor promoting breast cell cancer and the tumor stage. Aim: this study aimed to explore the hypermethylation of the BRCA1/2 promoter gene in breast cancer women and correlation with age and tumor stage.Materials and methods: fifty biopsies were derived from Moroccan women treated for breast carcinoma, the DNA extracted was treated by bisulphite and the targeted BRCA1/2 Amplicons were amplified by specific methylation primers (MSP). Results: the result shows that 62% of the samples were BRCA1 methylated in addition and negative result for BRCA2, these positive epigenetic factor were remarkable in women over 47 years and at the stage of malignant tumor.Conclusion: these results show that half of the methylated samples are positive and the majority are over 47 years old, and confirms the impact of age on methylation and might be other factor of breast cancer development.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2359
Author(s):  
Maria Elena Capra ◽  
Cristina Pederiva ◽  
Claudia Viggiano ◽  
Raffaella De Santis ◽  
Giuseppe Banderali ◽  
...  

Coronary Heart Disease (CHD) is a major mortality and morbidity cause in adulthood worldwide. The atherosclerotic process starts even before birth, progresses through childhood and, if not stopped, eventually leads to CHD. Therefore, it is important to start prevention from the earliest stages of life. CHD prevention can be performed at different interventional stages: primordial prevention is aimed at preventing risk factors, primary prevention is aimed at early identification and treatment of risk factors, secondary prevention is aimed at reducing the risk of further events in those patients who have already experienced a CHD event. In this context, CHD risk stratification is of utmost importance, in order to tailor the preventive and therapeutic approach. Nutritional intervention is the milestone treatment in pediatric patients at increased CHD risk. According to the Developmental Origin of Health and Disease theory, the origins of lifestyle-related disease is formed in the so called “first thousand days” from conception, when an insult, either positive or negative, can cause life-lasting consequences. Nutrition is a positive epigenetic factor: an adequate nutritional intervention in a developmental critical period can change the outcome from childhood into adulthood.


2021 ◽  
Vol 3 (5) ◽  
pp. 01-08
Author(s):  
P D Gupta

Microbiota is a life line for human being, however if the balance in interspecies of microbiota is disturb, it can cause not only serious diseases but can kill also. Collectively the microbiotal species act as epigenetic factor for humans. First exposure to microbiota is in utero. The whole health programming of the individuals stars even before birth. C-section or fed formula fed babies are immunologically weaker than that of normal delivered and beast fed babies. For the lifelong good health of babies, Mothers should opt for vaginal delivery and breastfeeding for healthy newborn


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