DNA methylation is a key epigenetic mechanism that mediates gene expression and informs cellular identity. Methyl-CpG binding protein 2 (MeCP2) is a protein capable of recognizing and interpreting the methylated DNA code to bring about phenotypic outcomes through co-factor interactions. Altered DNA methylation patterns and MeCP2 function, therefore, disrupt cellular epigenetic homeostasis and contribute to human diseases. MeCP2 loss-of-function or amplification events are responsible for Rett syndrome and MECP2 duplication syndrome, respectively, where patients present with multisystem pathophysiology. Growing evidence suggests that MeCP2 contributes to immune dysregulation in these syndromes and is a key epigenetic regulator in additional inflammatory conditions. Research in past decades has functionally linked MeCP2 to tumorigenesis across cancer types, where it can support and inhibit oncogenic properties in a contextual manner. The precise mechanistic role of MeCP2 in non-neuronal and cancer models is underexplored. Here, we summarize the diverse epigenetic functionalities of MeCP2 influenced by its molecular structure, regulation, and co-factor interactions and discuss how MeCP2 regulates immune homeostasis and tumorigenesis.
Pathogenic variation can alter gene output at multiple levels, from chromatin accessibility and enhancer-promoter communication to RNA processing, translation and protein turnover. The diagnostic challenge is not to catalogue these layers, but to determine which regulatory mechanism is plausible for a given variant, phenotype, tissue and developmental context. This targeted narrative review synthesises representative Mendelian mechanisms across five linked levels: chromatin, transcription, RNA processing and stability, translation, and post-translational proteostasis. Three cross-cutting principles recur. First, distinct molecular lesions may converge on the same functional bottleneck: altered dosage, timing, localisation or disrupted protein homeostasis. Second, regulatory effects are often cell-type-, isoform-, developmental-stage- and state-specific, so assay and tissue selection are integral to interpretation. Third, a negative result in an accessible surrogate such as blood does not exclude a disease-relevant effect in brain, muscle, liver or stimulated immune cells. From these principles, the review derives a mechanism-directed diagnostic framework that links variant class to orthogonal assays, including DNA methylation profiling, chromatin and reporter assays, RNA sequencing, ribosome-level methods and protein-based studies. The framework is offered as an integrative clinical synthesis rather than a new model of gene regulation, to support variant interpretation, functional-test selection and translational prioritisation in unsolved Mendelian disease.
Circular RNAs (circRNAs) are single stranded, closed, primarily non-coding RNA circles that have risen to the forefront of the non-coding RNA field. Studies from recent years have shown that circRNAs are produced from endogenous, non-canonical RNA splicing mechanisms, demonstrate specific cellular localizations, regulation by RNA modifications and function in many fundamental and critical cellular processes. CircRNAs can influence gene expression both pre- and post-transcriptionally, influence translation and interact with cellular RNA and proteins to enable cellular homeostasis. Aberrations in circRNA expression patterns lead to alterations in gene regulatory networks, which have been implicated in the progression of many cancer types. Unique characteristics of circRNAs, particularly their stability within cells and ability to be leveraged for protein production, have led to the engineering of artificial circRNAs to be used as an emerging therapeutic modality. Here we review how circRNAs regulate homeostasis in normal tissues, how dysregulated expression of circRNAs impacts various cancers and emerging therapeutic technologies that build upon their unique features.
A key stage in the development of almost all types of malignancies is the dysregulation of telomeres and telomerase (hTERT). It has been suggested that arsenic-mediated changes in gene methylation status can mute tumor suppressor genes or increase oncogene expression, resulting in long-term alterations in the activity of genes governing cell transformation. Recent study demonstrated that, long-term exposure to an environmentally relevant dose of arsenic affects cellular development by interfering with the Hippo signaling system. The current study’s objective is to ascertain the underlying molecular cause of arsenic induced telomerase alteration and how it is associated with gene methylation. Twenty-eight female with intermittent breast cancer from arsenic exposed areas were selected, after surgery, a sample of the tumor and the healthy tissue (which serves as a control group) were extracted for further processing. Arsenic concentration was analyzed by atomic absorption spectrometry. Western blotting and RT-PCR were used to analyze the telomerase expression. Additionally, MS-PCR was used to identify the genetic and epigenetic changes, respectively. According to our research, 65% of female breast cancer patients had extremely high arsenic concentrations with elevated telomerase expression. The cause of this up regulation of telomerase expression is hTERT promoter hypomethylation. The findings also demonstrated a substantial association between breast cancer patients’ upregulation of hTERT and their exposure to arsenic and fine-needle biopsy specimens may provide further predictive information. Higher telomerase expression was associated with a worse outcome.
Fish cell lines have long supported aquatic research, yet their emerging role as seed cells for cultured seafood requires a deeper understanding of their phenotypic stability. Although these cells often demonstrate prolonged proliferation and relative resistance to culture-associated senescence, they can also exhibit marked culture-dependent variability. In this review, I examine a central feature of fish cell culture: the coexistence of durable growth and flexible cell states. By focusing on spontaneous immortalization, passage-dependent changes, and differentiation-related plasticity, particularly in muscle and adipose lineages, I consider how these phenomena may be interpreted through the lens of epigenetic plasticity. Direct epigenomic evidence remains limited, and this review therefore presents a hypothesis-generating conceptual framework rather than an established mechanistic model. Nevertheless, studies involving DNA demethylation, incomplete senescence programs, possible differences in senescence-related genomic context, environmental epigenetics, and nuclear organization provide conceptual clues that reversible regulatory processes above the level of DNA sequence may shape fish cell-state behavior. I further discuss how this perspective is relevant to aquatic biotechnology and cultured seafood, where reproducibility, lineage control, quality control, and process standardization depend on monitoring cell-state behavior while distinguishing reversible regulatory changes from genetic alterations acquired during long-term culture. Clarifying the regulatory processes associated with phenotypic plasticity in fish cell lines may therefore provide a useful foundation for future epigenomic studies and for the development of biologically reliable fish cell platforms.
