Histone modifications in diseases

Fernandes, Mónica T.; Almeida-Lousada, Hélder; Castelo‐Branco, Pedro

doi:10.1016/b978-0-12-816422-8.00001-5

Cited by 7 publications

(6 citation statements)

References 142 publications

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“…Indeed, the epigenetic code plays a crucial role in orchestrating most DNA-related processes. Non-physiological levels of histone modifications are common in various human diseases—e.g., autoimmune diseases, neurodegenerative diseases, cardiovascular diseases, and cancer 3 —and, as such, are often involved in the prognosis process 4 . For example, in the context of breast cancer, the imbalance of acetylation and methylation of histone tails results in an unusual opening or closing of the chromatin structure 5 , and several other epigenetic marks, e.g.…”

Section: Introductionmentioning

confidence: 99%

Imaging-based study demonstrates how the DEK nanoscale distribution differentially correlates with epigenetic marks in a breast cancer model

Pierzynska-Mach,

Cainero,

Oneto

et al. 2023

Sci Rep

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Epigenetic dysregulation of chromatin is one of the hallmarks of cancer development and progression, and it is continuously investigated as a potential general bio-marker of this complex disease. One of the nuclear factors involved in gene regulation is the unique DEK protein—a histone chaperon modulating chromatin topology. DEK expression levels increase significantly from normal to cancer cells, hence raising the possibility of using DEK as a tumor marker. Although DEK is known to be implicated in epigenetic and transcriptional regulation, the details of these interactions and their relevance in cancer development remain largely elusive. In this work, we investigated the spatial correlation between the nuclear distribution of DEK and chromatin patterns—alongside breast cancer progression—leveraging image cross-correlation spectroscopy (ICCS) coupled with Proximity Ligation Assay (PLA) analysis. We performed our study on the model based on three well-established human breast cell lines to consider this tumor's heterogeneity (MCF10A, MCF7, and MDA-MB-231 cells). Our results show that overexpression of DEK correlates with the overall higher level of spatial proximity between DEK and histone marks corresponding to gene promoters regions (H3K9ac, H3K4me3), although it does not correlate with spatial proximity between DEK and gene enhancers (H3K27ac). Additionally, we observed that colocalizing fractions of DEK and histone marks are lower for the non-invasive cell subtype than for the highly invasive cell line (MDA-MB-231). Thus, this study suggests that the role of DEK on transcriptionally active chromatin regions varies depending on the subtype of the breast cancer cell line.

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Section: Introductionmentioning

confidence: 99%

Imaging-based study demonstrates how the DEK nanoscale distribution differentially correlates with epigenetic marks in a breast cancer model

Pierzynska-Mach,

Cainero,

Oneto

et al. 2023

Sci Rep

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“…These changes affect the interaction between different histones as well as DNA by altering availability of binding sites for specific protein complexes, including histone‐modifying enzymes, transcription factors, and hence regulating the gene expression. Although aberrant histone modifications like acetylation and methylation are extensively researched in association with pathogenesis of many diseases, including cancers, neurodegenerative diseases, autoimmune diseases, and so forth, [ 17–19 ] but a functional understanding of several modifications, alone or in combination, is still lacking (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Effect of lead exposure on histone modifications: A review

Kumar,

Anjali,

Sharma

2023

J Biochem & Molecular Tox

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Lead at any levels can result in detrimental health effects affecting various organ systems. These systematic manifestations under Pb exposure and the underlying probable pathophysiological mechanisms have not been elucidated completely. With advancements in molecular research under Pb exposure, epigenetics is one of the emerging field that has opened many possibilities for appreciating the role of Pb exposure in modulating gene expression profiles. In terms of epigenetic alterations reported in Pb toxicity, DNA methylation, and microRNA alterations are extensively explored in both experimental and epidemiological studies, however, the understanding of histone modifications under Pb exposure is still in its infant stage limited to experimental models. In this review, we aim to present a synoptic view of histone modifications explored in relation to Pb exposure attempting to bring out this potential lacunae in research. The scarcity of studies associating histone modifications with Pb toxicity, and the paucity of their validation in human cohort further emphasizes the strong research potential of this field. We summarize the review by presenting our hypotheses regarding the involvement of these histone modification in various diseases modalities associated with Pb toxicity

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“…Posttranslational modifications (PTMs) of histones, especially at their N-terminal tails, play important roles in regulating chromatin dynamics and a variety of DNA-templated biological processes. Dysregulation of these processes due to histone modifications is closely associated with the development of various diseases [ 2 , 3 ]. At least nine different types of histone modifications have been discovered.…”

Section: Introductionmentioning

confidence: 99%

Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC

Liang,

Wang,

et al. 2023

Clin Epigenet

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Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.

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Histone modifications in diseases

Cited by 7 publications

References 142 publications

Imaging-based study demonstrates how the DEK nanoscale distribution differentially correlates with epigenetic marks in a breast cancer model

Imaging-based study demonstrates how the DEK nanoscale distribution differentially correlates with epigenetic marks in a breast cancer model

Effect of lead exposure on histone modifications: A review

Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC

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