Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献_第2页

Uncovering the functions and mechanisms of regulatory elements-associated non-coding RNAs 揭示与调控元件相关的非编码 RNA 的功能和机制。

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-09-01 DOI: 10.1016/j.bbagrm.2024.195059

Olivier Fosseprez, Olivier Cuvier

{"title":"Uncovering the functions and mechanisms of regulatory elements-associated non-coding RNAs","authors":"Olivier Fosseprez, Olivier Cuvier","doi":"10.1016/j.bbagrm.2024.195059","DOIUrl":"10.1016/j.bbagrm.2024.195059","url":null,"abstract":"<div><p>Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195059"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000555/pdfft?md5=a719d7cce4914187f6a9ae2d68dbcc63&pid=1-s2.0-S1874939924000555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Normalization of gene counts affects principal components-based exploratory analysis of RNA-sequencing data 基因数量的归一化会影响基于主成分的 RNA 序列数据探索性分析。

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-08-16 DOI: 10.1016/j.bbagrm.2024.195058

Henk J. van Lingen, Maria Suarez-Diez, Edoardo Saccenti

{"title":"Normalization of gene counts affects principal components-based exploratory analysis of RNA-sequencing data","authors":"Henk J. van Lingen, Maria Suarez-Diez, Edoardo Saccenti","doi":"10.1016/j.bbagrm.2024.195058","DOIUrl":"10.1016/j.bbagrm.2024.195058","url":null,"abstract":"<div><p>Normalization of gene expression count data is an essential step of in the analysis of RNA-sequencing data. Its statistical analysis has been mostly addressed in the context of differential expression analysis, that is in the univariate setting. However, relationships among genes and samples are better explored and quantified using multivariate exploratory data analysis tools like Principal Component Analysis (PCA). In this study we investigate how normalization impacts the PCA model and its interpretation, considering twelve different widely used normalization methods that were applied on simulated and experimental data. Correlation patterns in the normalized data were explored using both summary statistics and Covariance Simultaneous Component Analysis. The impact of normalization on the PCA solution was assessed by exploring the model complexity, the quality of sample clustering in the low-dimensional PCA space and gene ranking in the model fit to normalized data. PCA models upon normalization were interpreted in the context gene enrichment pathway analysis. We found that although PCA score plots are often similar independently form the normalization used, biological interpretation of the models can depend heavily on the normalization method applied.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195058"},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000543/pdfft?md5=6c80095a6aa1d7d87e5ef95c4f8180b2&pid=1-s2.0-S1874939924000543-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crosstalk between circular RNAs and the STAT3 signaling pathway in human cancer 人类癌症中环状 RNA 与 STAT3 信号通路之间的相互影响

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-08-08 DOI: 10.1016/j.bbagrm.2024.195051

Mansour Almouh , Chadi Soukkarieh , Morshed Kassouha , Samer Ibrahim

{"title":"Crosstalk between circular RNAs and the STAT3 signaling pathway in human cancer","authors":"Mansour Almouh , Chadi Soukkarieh , Morshed Kassouha , Samer Ibrahim","doi":"10.1016/j.bbagrm.2024.195051","DOIUrl":"10.1016/j.bbagrm.2024.195051","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are endogenous covalently closed single-stranded RNAs produced by reverse splicing of pre-mRNA. Emerging evidence suggests that circRNAs contribute to cancer progression by modulating the oncogenic STAT3 signaling pathway, which plays key roles in human malignancies. STAT3 signaling-related circRNAs expression appears to be extensively dysregulated in diverse cancer types, where they function either as tumor suppressors or oncogenes. However, the biological effects of STAT3 signaling-related circRNAs and their associations with cancer have not been systematically studied before. Given this, shedding light on the interaction between circRNAs and STAT3 signaling pathway in human malignancies may provide several novel insights into cancer therapy. In this review, we provide a comprehensive introduction to the molecular mechanisms by which circRNAs regulate STAT3 signaling in cancer progression, and the crosstalk between STAT3 signaling-related circRNAs and other signaling pathways. We also further discuss the role of the circRNA/STAT3 axis in cancer chemotherapy sensitivity.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195051"},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human ARMC6 binds in vitro to both cancer genes and telomeric RNA, favoring G-quadruplex structure recognition 人类 ARMC6 在体外与癌基因和端粒 RNA 结合，有利于识别 G 型四联结构。

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-07-17 DOI: 10.1016/j.bbagrm.2024.195050

Matej Adámik , Zuzana Soldánová , Magdaléna Drotárová , Katarína Brečková , Marek Petr , Robert Helma , Leon P. Jenner , Michaela Vorlíčková , Eva Sýkorová , Marie Brázdová

{"title":"Human ARMC6 binds in vitro to both cancer genes and telomeric RNA, favoring G-quadruplex structure recognition","authors":"Matej Adámik , Zuzana Soldánová , Magdaléna Drotárová , Katarína Brečková , Marek Petr , Robert Helma , Leon P. Jenner , Michaela Vorlíčková , Eva Sýkorová , Marie Brázdová","doi":"10.1016/j.bbagrm.2024.195050","DOIUrl":"10.1016/j.bbagrm.2024.195050","url":null,"abstract":"<div><p>Armadillo repeat-containing proteins (ARMCs) are a large family found throughout eukaryotes, which play prominent roles in cell adhesion, signaling and cytoskeletal regulation. The ARMC6 protein is highly conserved in primates, including humans, but to date does not have a clear function beyond initial hints of a link to cancer and telomerase activity. We report here in vitro experiments showing ARMC6 binding to DNA promoter sequences from several cancer-related genes (e.g., <em>EGFR</em>, <em>VEGF</em> and c-<em>MYC)</em>, and also to the telomeric RNA repeat (TERRA). ARMC6 binding activity appears to recognize G-quadruplex motifs, which are being increasingly implicated as structure-based protein binding sites in chromosome maintenance and repair. In vivo investigation of ARMC6 function revealed that when this protein is overexpressed in human cell lines, there is different expression of genes connected with oncogenic pathways and those implicated in downstream non-canonical telomerase pathways (e.g., <em>VEGF</em>, <em>hTERT,</em> c-<em>MYC</em>, <em>ESM1</em>, <em>MMP3</em>). ARMC6 is already known to interact with human shelterin protein TRF2 and telomerase. The protein binds G-quadruplex structures and does so preferentially to RNA over DNA. As such, this protein may be an example of how a non-canonical nucleic acid structural motif allows mediation between gene regulation and telomeric chromatin rearrangement pathways.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195050"},"PeriodicalIF":2.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cut from the same cloth: RNAs transcribed from regulatory elements 一脉相承：从调控元件转录的 RNA

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-07-02 DOI: 10.1016/j.bbagrm.2024.195049

E.M. Stasevich , A.V. Simonova , E.A. Bogomolova , M.M. Murashko , A.N. Uvarova , E.A. Zheremyan , K.V. Korneev , A.M. Schwartz , D.V. Kuprash , D.E. Demin

{"title":"Cut from the same cloth: RNAs transcribed from regulatory elements","authors":"E.M. Stasevich , A.V. Simonova , E.A. Bogomolova , M.M. Murashko , A.N. Uvarova , E.A. Zheremyan , K.V. Korneev , A.M. Schwartz , D.V. Kuprash , D.E. Demin","doi":"10.1016/j.bbagrm.2024.195049","DOIUrl":"10.1016/j.bbagrm.2024.195049","url":null,"abstract":"<div><p>A certain degree of chromatin openness is necessary for the activity of transcription-regulating regions within the genome, facilitating accessibility to RNA polymerases and subsequent synthesis of regulatory element RNAs (regRNAs) from these regions. The rapidly increasing number of studies underscores the significance of regRNAs across diverse cellular processes and diseases, challenging the paradigm that these transcripts are non-functional transcriptional noise. This review explores the multifaceted roles of regRNAs in human cells, encompassing rather well-studied entities such as promoter RNAs and enhancer RNAs (eRNAs), while also providing insights into overshadowed silencer RNAs and insulator RNAs. Furthermore, we assess notable examples of shorter regRNAs, like miRNAs, snRNAs, and snoRNAs, playing important roles. Expanding our discourse, we deliberate on the potential usage of regRNAs as biomarkers and novel targets for cancer and other human diseases.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195049"},"PeriodicalIF":2.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

H3K56 acetylation affects Candida albicans morphology and secreted soluble factors interacting with the host H3K56 乙酰化影响白色念珠菌的形态以及与宿主相互作用的分泌型可溶性因子

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-06-15 DOI: 10.1016/j.bbagrm.2024.195048

Marisa Conte , Daniela Eletto , Martina Pannetta , Roberta Esposito , Maria Chiara Monti , Elva Morretta , Peter Tessarz , Silvana Morello , Alessandra Tosco , Amalia Porta

{"title":"H3K56 acetylation affects Candida albicans morphology and secreted soluble factors interacting with the host","authors":"Marisa Conte , Daniela Eletto , Martina Pannetta , Roberta Esposito , Maria Chiara Monti , Elva Morretta , Peter Tessarz , Silvana Morello , Alessandra Tosco , Amalia Porta","doi":"10.1016/j.bbagrm.2024.195048","DOIUrl":"10.1016/j.bbagrm.2024.195048","url":null,"abstract":"<div><p>In recent years, epigenetics has been revealed as a mechanism able to modulate the expression of virulence traits in diverse pathogens, including <em>Candida albicans</em>. Indeed, epigenetic regulation can sense environmental changes, leading to the rapid and reversible modulation of gene expression with consequent adaptation to novel environments. How epigenetic changes can impact expression and signalling output, including events associated with mechanisms of morphological transition and virulence, is still poorly studied. Here, using nicotinamide as a sirtuin inhibitor, we explored how the accumulation of the H3K56 acetylation, the most prominent histone acetylation in <em>C. albicans</em>, might affect its interaction with the host. Our experiments demonstrate that H3K56 acetylation profoundly affects the production and/or secretion of soluble factors compromising actin remodelling and cytokine production. ChIP- and RNA-seq analyses highlighted a direct impact of H3K56 acetylation on genes related to phenotypic switching, biofilm formation and cell aggregation. Direct and indirect regulation also involves genes related to cell wall protein biosynthesis, β-glucan and mannan exposure, and hydrolytic secreted enzymes, supporting the hypothesis that the fluctuations of H3K56 acetylation in <em>C. albicans</em> might impair the macrophage response to the yeast and thus promote the host-immune escaping.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195048"},"PeriodicalIF":2.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000440/pdfft?md5=8b63a578c5baa7bc3e34cab1b99bd9b7&pid=1-s2.0-S1874939924000440-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incautious design of shRNAs for stable overexpression of miRNAs could result in generation of undesired isomiRs 为稳定过表达 miRNA 而不谨慎地设计 shRNA 可能会导致产生不想要的等位 RNA。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-06-12 DOI: 10.1016/j.bbagrm.2024.195046

Diana Maltseva , Ivan Kirillov , Anton Zhiyanov , Daria Averinskaya , Roman Suvorov , Daria Gubani , Anna Kudriaeva , Alexey Belogurov Jr , Alexander Tonevitsky

{"title":"Incautious design of shRNAs for stable overexpression of miRNAs could result in generation of undesired isomiRs","authors":"Diana Maltseva , Ivan Kirillov , Anton Zhiyanov , Daria Averinskaya , Roman Suvorov , Daria Gubani , Anna Kudriaeva , Alexey Belogurov Jr , Alexander Tonevitsky","doi":"10.1016/j.bbagrm.2024.195046","DOIUrl":"10.1016/j.bbagrm.2024.195046","url":null,"abstract":"<div><p>shRNA-mediated strategy of miRNA overexpression based on RNA Polymerase III (Pol III) expression cassettes is widely used for miRNA functional studies. For some miRNAs, e.g., encoded in the genome as a part of a polycistronic miRNA cluster, it is most likely the only way for their individual stable overexpression. Here we have revealed that expression of miRNAs longer than 19 nt (e.g. 23 nt in length hsa-miR-93-5p) using such approach could be accompanied by undesired predominant generation of 5′ end miRNA isoforms (5′-isomiRs). Extra U residues (up to five) added by Pol III at the 3′ end of the transcribed shRNA during transcription termination could cause a shift in the Dicer cleavage position of the shRNA. This results in the formation of 5′-isomiRs, which have a significantly altered seed region compared to the initially encoded canonical hsa-miR-93-5p. We demonstrated that the commonly used qPCR method is insensitive to the formation of 5′-isomiRs and cannot be used to confirm miRNA overexpression. However, the predominant expression of 5′-isomiRs without three or four first nucleotides instead of the canonical isoform could be disclosed based on miRNA-Seq analysis. Moreover, mRNA sequencing data showed that the 5′-isomiRs of hsa-miR-93-5p presumably regulate their own mRNA targets. Thus, omitting miRNA-Seq analysis may lead to erroneous conclusions regarding revealed mRNA targets and possible molecular mechanisms in which studied miRNA is involved. Overall, the presented results show that structures of shRNAs for stable overexpression of miRNAs requires careful design to avoid generation of undesired 5′-isomiRs.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195046"},"PeriodicalIF":4.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HBO1, a MYSTerious KAT and its links to cancer HBO1，一种神秘的 KAT 及其与癌症的联系。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-06-06 DOI: 10.1016/j.bbagrm.2024.195045

Akihiko Yokoyama , Hiroyuki Niida , Tatiana G. Kutateladze , Jacques Côté

引用次数: 0

Histone ubiquitination: Role in genome integrity and chromatin organization 组蛋白泛素化：组蛋白泛素化：在基因组完整性和染色质组织中的作用

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-05-17 DOI: 10.1016/j.bbagrm.2024.195044

Nikhil Baban Ghate , Kaustubh Sanjay Nadkarni , Ganesh Kumar Barik , Sharad Shriram Tat , Osheen Sahay , Manas Kumar Santra

{"title":"Histone ubiquitination: Role in genome integrity and chromatin organization","authors":"Nikhil Baban Ghate , Kaustubh Sanjay Nadkarni , Ganesh Kumar Barik , Sharad Shriram Tat , Osheen Sahay , Manas Kumar Santra","doi":"10.1016/j.bbagrm.2024.195044","DOIUrl":"10.1016/j.bbagrm.2024.195044","url":null,"abstract":"<div><p>Maintenance of genome integrity is a precise but tedious and complex job for the cell. Several post-translational modifications (PTMs) play vital roles in maintaining the genome integrity. Although ubiquitination is one of the most crucial PTMs, which regulates the localization and stability of the nonhistone proteins in various cellular and developmental processes, ubiquitination of the histones is a pivotal epigenetic event critically regulating chromatin architecture. In addition to genome integrity, importance of ubiquitination of core histones (H2A, H2A, H3, and H4) and linker histone (H1) have been reported in several cellular processes. However, the complex interplay of histone ubiquitination and other PTMs, as well as the intricate chromatin architecture and dynamics, pose a significant challenge to unravel how histone ubiquitination safeguards genome stability. Therefore, further studies are needed to elucidate the interactions between histone ubiquitination and other PTMs, and their role in preserving genome integrity. Here, we review all types of histone ubiquitinations known till date in maintaining genomic integrity during transcription, replication, cell cycle, and DNA damage response processes. In addition, we have also discussed the role of histone ubiquitination in regulating other histone PTMs emphasizing methylation and acetylation as well as their potential implications in chromatin architecture. Further, we have also discussed the involvement of deubiquitination enzymes (DUBs) in controlling histone ubiquitination in modulating cellular processes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195044"},"PeriodicalIF":4.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

To Ub or not to Ub: The epic dilemma of histones that regulate gene expression and epigenetic cross-talk 要Ub还是不要Ub？组蛋白调控基因表达和表观遗传学交叉对话的两难困境。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-05-13 DOI: 10.1016/j.bbagrm.2024.195033

Anirban Dasgupta , Sandhik Nandi , Sayan Gupta , Siddhartha Roy , Chandrima Das

{"title":"To Ub or not to Ub: The epic dilemma of histones that regulate gene expression and epigenetic cross-talk","authors":"Anirban Dasgupta , Sandhik Nandi , Sayan Gupta , Siddhartha Roy , Chandrima Das","doi":"10.1016/j.bbagrm.2024.195033","DOIUrl":"10.1016/j.bbagrm.2024.195033","url":null,"abstract":"<div><p>A dynamic array of histone post-translational modifications (PTMs) regulate diverse cellular processes in the eukaryotic chromatin. Among them, histone ubiquitination is particularly complex as it alters nucleosome surface area fostering intricate cross-talk with other chromatin modifications. Ubiquitin signaling profoundly impacts DNA replication, repair, and transcription. Histones can undergo varied extent of ubiquitination such as mono, multi-mono, and polyubiquitination, which brings about distinct cellular fates. Mechanistic studies of the ubiquitin landscape in chromatin have unveiled a fascinating tapestry of events that orchestrate gene regulation. In this review, we summarize the key contributors involved in mediating different histone ubiquitination and deubiquitination events, and discuss their mechanism which impacts cell transcriptional identity and DNA damage response. We also focus on the proteins bearing epigenetic reader modules critical in discerning site-specific histone ubiquitination, pivotal for establishing complex epigenetic crosstalk. Moreover, we highlight the role of histone ubiquitination in different human diseases including neurodevelopmental disorders and cancer. Overall the review elucidates the intricate orchestration of histone ubiquitination impacting diverse cellular functions and disease pathogenesis, and provides insights into the current challenges of targeting them for therapeutic interventions.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195033"},"PeriodicalIF":4.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0