LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles

Li, Xiaojiaoyang; Zhou, Fei; Xue, Xiaoyong; Qu, Jiaorong; Fan, Guifang; Liu, Jia; Sun, Rong; Wu, Jianzhi; Zheng, Qi; Liu, Runping

doi:10.1038/s41401-023-01145-z

Cited by 11 publications

(2 citation statements)

References 43 publications

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“…The use of direct sequencing methods compatible with long reads will also be useful in the transcriptomics field ( Figure 2 ). So does current data suggest that the regulation of gene expression is provided in part by long noncoding RNAs (lncRNAs), that have no coding potential, regulate genes in cis via transcriptional interference and to a certain extend seem to be integrated into riboprotein complexes that mediate epigenetic modifications in predetermined genomic regions (e.g., H19 , a candidate for BWSp aspects) ( Li et al, 2023 ). As these lncRNAs may be larger than one kilobase, long read direct RNA-seq methods seem to be an appropriate approach.…”

Section: Discussion/perspectivesmentioning

confidence: 99%

Molecular mechanisms of human overgrowth and use of omics in its diagnostics: chances and challenges

Prawitt,

Eggermann

2024

Front. Genet.

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Overgrowth disorders comprise a group of entities with a variable phenotypic spectrum ranging from tall stature to isolated or lateralized overgrowth of body parts and or organs. Depending on the underlying physiological pathway affected by pathogenic genetic alterations, overgrowth syndromes are associated with a broad spectrum of neoplasia predisposition, (cardio) vascular and neurodevelopmental anomalies, and dysmorphisms. Pathologic overgrowth may be of prenatal or postnatal onset. It either results from an increased number of cells (intrinsic cellular hyperplasia), hypertrophy of the normal number of cells, an increase in interstitial spaces, or from a combination of all of these. The underlying molecular causes comprise a growing number of genetic alterations affecting skeletal growth and Growth-relevant signaling cascades as major effectors, and they can affect the whole body or parts of it (mosaicism). Furthermore, epigenetic modifications play a critical role in the manifestation of some overgrowth diseases. The diagnosis of overgrowth syndromes as the prerequisite of a personalized clinical management can be challenging, due to their clinical and molecular heterogeneity. Physicians should consider molecular genetic testing as a first diagnostic step in overgrowth syndromes. In particular, the urgent need for a precise diagnosis in tumor predisposition syndromes has to be taken into account as the basis for an early monitoring and therapy. With the (future) implementation of next-generation sequencing approaches and further omic technologies, clinical diagnoses can not only be verified, but they also confirm the clinical and molecular spectrum of overgrowth disorders, including unexpected findings and identification of atypical cases. However, the limitations of the applied assays have to be considered, for each of the disorders of interest, the spectrum of possible types of genomic variants has to be considered as they might require different methodological strategies. Additionally, the integration of artificial intelligence (AI) in diagnostic workflows significantly contribute to the phenotype-driven selection and interpretation of molecular and physiological data.

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Section: Discussion/perspectivesmentioning

confidence: 99%

Molecular mechanisms of human overgrowth and use of omics in its diagnostics: chances and challenges

Prawitt,

Eggermann

2024

Front. Genet.

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“…As a result, a diverse range of small molecule inhibitors explicitly targeting EZH2, along with several naturally occurring compounds exhibiting inhibitory effects on EZH2 activity, have been successfully developed[ 102 , 103 ]. Significantly, it has been demonstrated that treatment with DZNep effectively inhibits the proliferation of HSC-derived fibroblasts by modulating multiple histone methylation pathways[ 104 , 105 ]. Additionally, Xu et al [ 106 ] have provided evidence suggesting that pharmacological intervention targeting the methyltransferase Dot1L may represent a promising therapeutic approach for addressing diverse tissue fibrosis disorders in human subjects.…”

Section: Potential Clinical Application Of Histone Methylationmentioning

confidence: 99%

Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

Xu,

Fan,

Zhang

et al. 2024

World J Hepatol

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Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems from genetic predisposition, environmental influences, and metabolic factors. Epigenetic processes govern various cellular functions such as transcription, chromatin structure, and cell division. In NAFLD, these epigenetic tendencies, especially the process of histone methylation, are intricately intertwined with fat accumulation in the liver. Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis. While early-stage NAFLD is reversible, its progression to severe stages becomes almost irreversible. Therefore, early detection and intervention in NAFLD are crucial, and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

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An EED/PRC2‐H19 Loop Regulates Cerebellar Development

Liu,

Han,

et al. 2024

Advanced Science

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EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice. Joint profiling of transcripts and ChIP‐seq analysis in cerebellar granule cells reveals that EED regulates bunches of genes involved in cerebellar development. EED ablation exhibits overactivation of a developmental repressor long non‐coding RNA H19. Importantly, an obvious H3K27ac enrichment is found at Ctcf, a trans‐activator of H19, and H3K27me3 enrichment at the H19 imprinting control region (ICR), suggesting that EED regulates H19 in an H3K27me3‐dependent manner. Intriguingly, H19 deletion reduces EED expression and the reprogramming of EED‐mediated H3K27me3 profiles, resulting in increased proliferation, differentiation, and decreased apoptosis of GCPs. Finally, molecular and genetic evidence provides that increased H19 expression is responsible for cerebellar hypoplasia and motor defects in EED mutant mice. Thus, this study demonstrates that EED, H19 forms a negative feedback loop, which plays a crucial role in cerebellar morphogenesis and controls cerebellar development.

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LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles

Cited by 11 publications

References 43 publications

Molecular mechanisms of human overgrowth and use of omics in its diagnostics: chances and challenges

Molecular mechanisms of human overgrowth and use of omics in its diagnostics: chances and challenges

Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

An EED/PRC2‐H19 Loop Regulates Cerebellar Development

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