Current Opinion in Genetics & Development最新文献

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Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia KMT2A 重排急性淋巴细胞白血病中的染色质和异常增强子活性
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-04-04 DOI: 10.1016/j.gde.2024.102191
Thomas A Milne
{"title":"Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia","authors":"Thomas A Milne","doi":"10.1016/j.gde.2024.102191","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102191","url":null,"abstract":"<div><p>To make a multicellular organism, genes need to be transcribed at the right developmental stages and in the right tissues. DNA sequences termed ‘enhancers’ are crucial to achieve this. Despite concerted efforts, the exact mechanisms of enhancer activity remain elusive. <em>Mixed lineage leukemia</em> (<em>MLL</em> or <em>KMT2A</em>) rearrangements (MLLr), commonly observed in cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, produce novel in-frame fusion proteins. Recent work has shown that the MLL-AF4 fusion protein drives aberrant enhancer activity at key oncogenes in ALL, dependent on the continued presence of MLL-AF4 complex components. As well as providing some general insights into enhancer function, these observations may also provide an explanation for transcriptional heterogeneity observed in MLLr patients.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102191"},"PeriodicalIF":4.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000406/pdfft?md5=a5161d94b242766d396add9a0de2fd94&pid=1-s2.0-S0959437X24000406-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140348130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Therapeutic targeting of BET bromodomain and other epigenetic acetylrecognition domain–containing factors 以 BET 溴化结构域和其他含乙酰基识别结构域的表观遗传因子为治疗靶点
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-04-02 DOI: 10.1016/j.gde.2024.102181
Sarah Gold , Ali Shilatifard
{"title":"Therapeutic targeting of BET bromodomain and other epigenetic acetylrecognition domain–containing factors","authors":"Sarah Gold ,&nbsp;Ali Shilatifard","doi":"10.1016/j.gde.2024.102181","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102181","url":null,"abstract":"<div><p>Development of cancer therapies targeting chromatin modifiers and transcriptional regulatory factors is rapidly expanding to include new targets and novel targeting strategies. At the same time, basic molecular research continues to refine our understanding of the epigenetic mechanisms regulating transcription, gene expression, and oncogenesis. This mini-review focuses on cancer therapies targeting the chromatin-associated factors that recognize histone lysine acetylation. Recently reported safety and efficacy are discussed for inhibitors targeting the bromodomains of bromodomain and extraterminal domain (BET) family proteins. In light of recent results indicating that the transcriptional regulator BRD4-PTEFb can function independently of BRD4’s bromodomains, the clinical trial performance of these BET inhibitors is placed in a broader context of existing and potential strategies for targeting BRD4-PTEFb. Recently developed therapies targeting bromodomain-containing factors within the SWI/SNF (BAF) family of chromatin remodeling complexes are discussed, as is the potential for targeting the bromodomain-containing transcription factor TAF1 and the YEATS acetylrecognition domain–containing factor GAS41. Recent findings regarding the selectivity and combinatorial specificity of acetylrecognition are highlighted. In conclusion, the potential for further development is discussed with a focus on proximity-based therapies targeting this class of epigenetic factors.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102181"},"PeriodicalIF":4.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Linking mitochondria metabolism, developmental timing, and human brain evolution 将线粒体代谢、发育时间与人类大脑进化联系起来
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-30 DOI: 10.1016/j.gde.2024.102182
Pierre Casimir , Ryohei Iwata , Pierre Vanderhaeghen
{"title":"Linking mitochondria metabolism, developmental timing, and human brain evolution","authors":"Pierre Casimir ,&nbsp;Ryohei Iwata ,&nbsp;Pierre Vanderhaeghen","doi":"10.1016/j.gde.2024.102182","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102182","url":null,"abstract":"<div><p>Changes in developmental timing are an important factor of evolution in organ shape and function. This is particularly striking for human brain development, which, compared with other mammals, is considerably prolonged at the level of the cerebral cortex, resulting in brain neoteny. Here, we review recent findings that indicate that mitochondria and metabolism contribute to species differences in the tempo of cortical neuron development. Mitochondria display species-specific developmental timeline and metabolic activity patterns that are highly correlated with the speed of neuron maturation. Enhancing mitochondrial activity in human cortical neurons results in their accelerated maturation, while its reduction leads to decreased maturation rates in mouse neurons. Together with other global and gene-specific mechanisms, mitochondria thus act as a cellular hourglass of neuronal developmental tempo and may thereby contribute to species-specific features of human brain ontogeny.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102182"},"PeriodicalIF":4.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000315/pdfft?md5=77551de0737d6c44e46c6a8b5dbf0cd1&pid=1-s2.0-S0959437X24000315-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The significance of ultradian oscillations in development 昼夜节律振荡在发育过程中的意义
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-23 DOI: 10.1016/j.gde.2024.102180
Yuki Maeda, Ryoichiro Kageyama
{"title":"The significance of ultradian oscillations in development","authors":"Yuki Maeda,&nbsp;Ryoichiro Kageyama","doi":"10.1016/j.gde.2024.102180","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102180","url":null,"abstract":"<div><p>Genes regulating developmental processes have been identified, but the mechanisms underlying their expression with the correct timing are still under investigation. Several genes show oscillatory expression that regulates the timing of developmental processes, such as somitogenesis and neurogenesis. These oscillations are also important for other developmental processes, such as cell proliferation and differentiation. In this review, we discuss the significance of oscillatory gene expression in developmental time and other forms of regulation.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102180"},"PeriodicalIF":4.0,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
RNA in chromatin organization and nuclear architecture 染色质组织和核结构中的 RNA
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-14 DOI: 10.1016/j.gde.2024.102176
Maierdan Palihati, Noriko Saitoh
{"title":"RNA in chromatin organization and nuclear architecture","authors":"Maierdan Palihati,&nbsp;Noriko Saitoh","doi":"10.1016/j.gde.2024.102176","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102176","url":null,"abstract":"<div><p>In the cell nucleus, genomic DNA is surrounded by nonmembranous nuclear bodies. This might result from specific regions of the genome being transcribed into long noncoding RNAs (lncRNAs), which tend to remain at the sites of their own transcription. The lncRNAs seed the nuclear bodies by recruiting and concentrating proteins and RNAs, which undergo liquid–liquid-phase separation, and form molecular condensates, the so-called nuclear bodies. These nuclear bodies may provide appropriate environments for gene activation or repression. Notably, lncRNAs also contribute to three-dimensional genome structure by mediating long-range chromatin interactions. In this review, we discuss the mechanisms by which lncRNAs regulate gene expression through shaping chromatin and nuclear architectures. We also explore lncRNAs’ potential as a therapeutic target for cancer, because lncRNAs are often expressed in a disease-specific manner.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102176"},"PeriodicalIF":4.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Temporal patterning of the vertebrate developing neural tube 脊椎动物发育中神经管的时间模式
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-14 DOI: 10.1016/j.gde.2024.102179
Andreas Sagner
{"title":"Temporal patterning of the vertebrate developing neural tube","authors":"Andreas Sagner","doi":"10.1016/j.gde.2024.102179","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102179","url":null,"abstract":"<div><p>The chronologically ordered generation of distinct cell types is essential for the establishment of neuronal diversity and the formation of neuronal circuits. Recently, single-cell transcriptomic analyses of various areas of the developing vertebrate nervous system have provided evidence for the existence of a shared temporal patterning program that partitions neurons based on the timing of neurogenesis. In this review, I summarize the findings that lead to the proposal of this shared temporal program before focusing on the developing spinal cord to discuss how temporal patterning in general and this program specifically contributes to the ordered formation of neuronal circuits.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102179"},"PeriodicalIF":4.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000285/pdfft?md5=39674796de47b5af51eb9e42c92db5a3&pid=1-s2.0-S0959437X24000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mitochondrial metabolism and the continuing search for ultimate regulators of developmental rate 线粒体新陈代谢和继续寻找发育速度的最终调节因素。
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-10 DOI: 10.1016/j.gde.2024.102178
Margarete Diaz-Cuadros
{"title":"Mitochondrial metabolism and the continuing search for ultimate regulators of developmental rate","authors":"Margarete Diaz-Cuadros","doi":"10.1016/j.gde.2024.102178","DOIUrl":"10.1016/j.gde.2024.102178","url":null,"abstract":"<div><p>The rate of embryonic development is a species-specific trait that depends on the properties of the intracellular environment, namely, the rate at which gene products flow through the central dogma of molecular biology. Although any given step in the production and degradation of gene products could theoretically be co-opted by evolution to modulate developmental speed, species are observed to accelerate or slow down all steps simultaneously. This suggests the rate of these molecular processes is jointly regulated by an upstream, ultimate factor. Mitochondrial metabolism was recently proposed to act as an ultimate regulator by controlling the pace of protein synthesis upstream of developmental tempo. Alternative candidates for ultimate regulators include species-specific gene expression levels of factors involved in the central dogma, as well as species-specific cell size. Overall, much work remains to be done before we can confidently identify the ultimate causes of species-specific developmental rates.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102178"},"PeriodicalIF":4.0,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Dynamic microenvironments shape nuclear organization and gene expression 动态微环境塑造核组织和基因表达。
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-10 DOI: 10.1016/j.gde.2024.102177
Gabriela Hayward-Lara , Matthew D Fischer , Mustafa Mir
{"title":"Dynamic microenvironments shape nuclear organization and gene expression","authors":"Gabriela Hayward-Lara ,&nbsp;Matthew D Fischer ,&nbsp;Mustafa Mir","doi":"10.1016/j.gde.2024.102177","DOIUrl":"10.1016/j.gde.2024.102177","url":null,"abstract":"<div><p>Live imaging has revealed that the regulation of gene expression is largely driven by transient interactions. For example, many regulatory proteins bind chromatin for just seconds, and loop-like genomic contacts are rare and last only minutes. These discoveries have been difficult to reconcile with our canonical models that are predicated on stable and hierarchical interactions. Proteomic microenvironments that concentrate nuclear factors may explain how brief interactions can still mediate gene regulation by creating conditions where reactions occur more frequently. Here, we summarize new imaging technologies and recent discoveries implicating microenvironments as a potential driver of nuclear function. Finally, we propose that key properties of proteomic microenvironments, such as their size, enrichment, and lifetimes, are directly linked to regulatory function.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102177"},"PeriodicalIF":4.0,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Safeguarding the epigenome through the cell cycle: a multitasking game 通过细胞周期保护表观基因组:多任务游戏
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-05 DOI: 10.1016/j.gde.2024.102161
Valentin Flury , Anja Groth
{"title":"Safeguarding the epigenome through the cell cycle: a multitasking game","authors":"Valentin Flury ,&nbsp;Anja Groth","doi":"10.1016/j.gde.2024.102161","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102161","url":null,"abstract":"<div><p>Sustaining cell identity and function across cell division is germane to human development, healthspan, and cancer avoidance. This relies significantly on propagation of chromatin organization between cell generations, as chromatin presents a barrier to cell fate and cell state conversions. Inheritance of chromatin states across the many cell divisions required for development and tissue homeostasis represents a major challenge, especially because chromatin is disrupted to allow passage of the DNA replication fork to synthesize the two daughter strands. This process also leads to a twofold dilution of epigenetic information in histones, which needs to be accurately restored for faithful propagation of chromatin states across cell divisions. Recent research has identified distinct multilayered mechanisms acting to propagate epigenetic information to daughter strands. Here, we summarize key principles of how epigenetic information in parental histones is transferred across DNA replication and how new histones robustly acquire the same information postreplication, representing a core component of epigenetic cell memory.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102161"},"PeriodicalIF":4.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000108/pdfft?md5=f69265aac37da46bcc617ee5f1a72472&pid=1-s2.0-S0959437X24000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140042809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Timers, variability, and body-wide coordination: C. elegans as a model system for whole-animal developmental timing 定时器、可变性和全身协调:作为整个动物发育定时模型系统的眼镜蛇
IF 4 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-03-02 DOI: 10.1016/j.gde.2024.102172
Gouri Patil, Jeroen S van Zon
{"title":"Timers, variability, and body-wide coordination: C. elegans as a model system for whole-animal developmental timing","authors":"Gouri Patil,&nbsp;Jeroen S van Zon","doi":"10.1016/j.gde.2024.102172","DOIUrl":"https://doi.org/10.1016/j.gde.2024.102172","url":null,"abstract":"<div><p>Successful development requires both precise timing of cellular processes, such as division and differentiation, and tight coordination of timing between tissues and organs. Yet, how time information is encoded with high precision and synchronized between tissues, despite inherent molecular noise, is unsolved. Here, we propose the nematode <em>C. elegans</em> as a unique model system for studying body-wide control of developmental timing. Recent studies combining genetics, quantitative analysis, and simulations have 1) mapped core timers controlling larval development, indicating temporal gradients as an underlying mechanism, and 2) elucidated general principles that make timing insensitive to inherent fluctuations and variation in environmental conditions. As the molecular regulators of <em>C. elegans</em> developmental timing are broadly conserved, these mechanisms likely apply also to higher organisms.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"85 ","pages":"Article 102172"},"PeriodicalIF":4.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000212/pdfft?md5=b9fe5d86bf25466d6e8d8c39fdea7659&pid=1-s2.0-S0959437X24000212-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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