Pub Date : 2025-01-16DOI: 10.1016/j.molcel.2024.12.020
Demis Menolfi
Section snippets
Main text
Patterns can be broadly defined as regular repetitions in contrast to random or casual arrangements. They are associated with order and are often governed by underlying rules. Close inspection of the natural world reveals pervasive patterns that are more common than one might think. For example, macroscopic patterns in the animal and plant kingdoms appear in the stripes of a zebra or the spiral arrangement of a pinecone’s scales. In the microscopic world, the internal organization of cells
{"title":"Exploring patterns in molecular biology","authors":"Demis Menolfi","doi":"10.1016/j.molcel.2024.12.020","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.020","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Patterns can be broadly defined as regular repetitions in contrast to random or casual arrangements. They are associated with order and are often governed by underlying rules. Close inspection of the natural world reveals pervasive patterns that are more common than one might think. For example, macroscopic patterns in the animal and plant kingdoms appear in the stripes of a zebra or the spiral arrangement of a pinecone’s scales. In the microscopic world, the internal organization of cells</section></section>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"37 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1016/j.molcel.2024.12.019
Leandro N. Ventimiglia, Aleksej Zelezniak
In a recent study in Nature, Gosai et al.1 introduce a framework to engineer and validate synthetic DNA regulatory elements showing cell-type-specific activity in human cell lines, closing the distance to the machine-driven design of functional regulatory sequences with therapeutic applications in humans.
在最近发表于《自然》（Nature）的一项研究中，Gosai 等人1 提出了一个框架，用于设计和验证在人类细胞系中显示出细胞类型特异性活性的合成 DNA 调控元件，从而拉近了机器驱动的功能性调控序列设计与人类治疗应用之间的距离。
{"title":"Programming of synthetic regulatory DNA for cell-type targeting in humans","authors":"Leandro N. Ventimiglia, Aleksej Zelezniak","doi":"10.1016/j.molcel.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.019","url":null,"abstract":"In a recent study in <em>Nature</em>, Gosai et al.<span><span><sup>1</sup></span></span> introduce a framework to engineer and validate synthetic DNA regulatory elements showing cell-type-specific activity in human cell lines, closing the distance to the machine-driven design of functional regulatory sequences with therapeutic applications in humans.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"24 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1016/j.molcel.2024.10.035
Zhiming Li, Zhiguo Zhang
DNA replication, a fundamental process in all living organisms, proceeds with continuous synthesis of the leading strand by DNA polymerase ε (Pol ε) and discontinuous synthesis of the lagging strand by polymerase δ (Pol δ). This inherent asymmetry at each replication fork necessitates the development of methods to distinguish between these two nascent strands in vivo. Over the past decade, strand-specific sequencing strategies, such as enrichment and sequencing of protein-associated nascent DNA (eSPAN) and Okazaki fragment sequencing (OK-seq), have become essential tools for studying chromatin replication in eukaryotic cells. In this review, we outline the foundational principles underlying these methodologies and summarize key mechanistic insights into DNA replication, parental histone transfer, epigenetic inheritance, and beyond, gained through their applications. Finally, we discuss the limitations and challenges of current techniques, highlighting the need for further technological innovations to better understand the dynamics and regulation of chromatin replication in eukaryotic cells.
{"title":"A tale of two strands: Decoding chromatin replication through strand-specific sequencing","authors":"Zhiming Li, Zhiguo Zhang","doi":"10.1016/j.molcel.2024.10.035","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.10.035","url":null,"abstract":"DNA replication, a fundamental process in all living organisms, proceeds with continuous synthesis of the leading strand by DNA polymerase ε (Pol ε) and discontinuous synthesis of the lagging strand by polymerase δ (Pol δ). This inherent asymmetry at each replication fork necessitates the development of methods to distinguish between these two nascent strands <em>in vivo</em>. Over the past decade, strand-specific sequencing strategies, such as enrichment and sequencing of protein-associated nascent DNA (eSPAN) and Okazaki fragment sequencing (OK-seq), have become essential tools for studying chromatin replication in eukaryotic cells. In this review, we outline the foundational principles underlying these methodologies and summarize key mechanistic insights into DNA replication, parental histone transfer, epigenetic inheritance, and beyond, gained through their applications. Finally, we discuss the limitations and challenges of current techniques, highlighting the need for further technological innovations to better understand the dynamics and regulation of chromatin replication in eukaryotic cells.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"75 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1016/j.molcel.2024.12.012
Varun Sahu, Chao Lu
Cells integrate metabolic information into core molecular processes such as transcription to adapt to environmental changes. Chromatin, the physiological template of the eukaryotic genome, has emerged as a sensor and rheostat for fluctuating intracellular metabolites. In this review, we highlight the growing list of chromatin-associated metabolites that are derived from diverse sources. We discuss recent advances in our understanding of the mechanisms by which metabolic enzyme activities shape the chromatin structure and modifications, how specificity may emerge from their seemingly broad effects, and technologies that facilitate the study of epigenome-metabolome interplay. The recognition that metabolites are immanent components of the chromatin regulatory network has significant implications for the evolution, function, and therapeutic targeting of the epigenome.
{"title":"Metabolism-driven chromatin dynamics: Molecular principles and technological advances","authors":"Varun Sahu, Chao Lu","doi":"10.1016/j.molcel.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.012","url":null,"abstract":"Cells integrate metabolic information into core molecular processes such as transcription to adapt to environmental changes. Chromatin, the physiological template of the eukaryotic genome, has emerged as a sensor and rheostat for fluctuating intracellular metabolites. In this review, we highlight the growing list of chromatin-associated metabolites that are derived from diverse sources. We discuss recent advances in our understanding of the mechanisms by which metabolic enzyme activities shape the chromatin structure and modifications, how specificity may emerge from their seemingly broad effects, and technologies that facilitate the study of epigenome-metabolome interplay. The recognition that metabolites are immanent components of the chromatin regulatory network has significant implications for the evolution, function, and therapeutic targeting of the epigenome.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"30 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1016/j.molcel.2024.12.024
Paul Wijnhoven, Rebecca Konietzny, Andrew N. Blackford, Jonathan Travers, Benedikt M. Kessler, Ryotaro Nishi, Stephen P. Jackson
(Molecular Cell 60, 362–373; November 5, 2015)
(分子细胞》60期，362-373页；2015年11月5日）
{"title":"USP4 Auto-Deubiquitylation Promotes Homologous Recombination","authors":"Paul Wijnhoven, Rebecca Konietzny, Andrew N. Blackford, Jonathan Travers, Benedikt M. Kessler, Ryotaro Nishi, Stephen P. Jackson","doi":"10.1016/j.molcel.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.024","url":null,"abstract":"(Molecular Cell <em>60</em>, 362–373; November 5, 2015)","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"96 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.molcel.2024.12.023
Xiang Zheng, Andreas Mund, Matthias Mann
Deciphering the intricate tumor-immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we introduce mipDVP, an advanced approach integrating highly multiplexed imaging, single-cell laser microdissection, and sensitive mass spectrometry to spatially profile the proteomes of distinct cell populations in a human colorectal and tonsil cancer with high sensitivity. In a colorectal tumor—a representative cold tumor—we uncovered spatial compartmentalization of an immunosuppressive macrophage barrier that potentially impedes T cell infiltration. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In a tonsil cancer sample—a hot tumor—we identified significant proteomic heterogeneity among cells influenced by proximity to cytotoxic T cell subtypes. T cells in the tumor parenchyma exhibit metabolic adaptations to hypoxic regions. Our spatially resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, offering valuable insights for identifying immunotherapy targets and predictive signatures.
{"title":"Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics","authors":"Xiang Zheng, Andreas Mund, Matthias Mann","doi":"10.1016/j.molcel.2024.12.023","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.023","url":null,"abstract":"Deciphering the intricate tumor-immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we introduce mipDVP, an advanced approach integrating highly multiplexed imaging, single-cell laser microdissection, and sensitive mass spectrometry to spatially profile the proteomes of distinct cell populations in a human colorectal and tonsil cancer with high sensitivity. In a colorectal tumor—a representative cold tumor—we uncovered spatial compartmentalization of an immunosuppressive macrophage barrier that potentially impedes T cell infiltration. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In a tonsil cancer sample—a hot tumor—we identified significant proteomic heterogeneity among cells influenced by proximity to cytotoxic T cell subtypes. T cells in the tumor parenchyma exhibit metabolic adaptations to hypoxic regions. Our spatially resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, offering valuable insights for identifying immunotherapy targets and predictive signatures.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"22 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.molcel.2024.12.017
Jiangfeng Zhao, Daniel Peter, Irina Brandina, Xiangyang Liu, Wojciech P. Galej
The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5′ splice site (5′SS) recognition. SNRNP25 and SNRNP35 specifically recognize U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48, located at the distal ends of the particle. SNRNP48 and ZMAT5 are positioned near the 5′ end of U11 snRNA and stabilize binding of the incoming 5′SS. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of the U11 snRNA and unexpected, non-canonical base-triple interactions with the U11 snRNA stem-loop 3. Our structures provide mechanistic insights into U12-dependent intron recognition and the evolution of the splicing machinery.
{"title":"Structural basis of 5′ splice site recognition by the minor spliceosome","authors":"Jiangfeng Zhao, Daniel Peter, Irina Brandina, Xiangyang Liu, Wojciech P. Galej","doi":"10.1016/j.molcel.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.017","url":null,"abstract":"The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5′ splice site (5′SS) recognition. SNRNP25 and SNRNP35 specifically recognize U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48, located at the distal ends of the particle. SNRNP48 and ZMAT5 are positioned near the 5′ end of U11 snRNA and stabilize binding of the incoming 5′SS. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of the U11 snRNA and unexpected, non-canonical base-triple interactions with the U11 snRNA stem-loop 3. Our structures provide mechanistic insights into U12-dependent intron recognition and the evolution of the splicing machinery.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"29 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres in aged human fibroblasts and tissues and in various cellular senescent models. Our findings reveal that the centromeric histone H3 variant CENP-A is downregulated in aged cells in a p53-dependent manner. We observe repression of centromeric noncoding transcription through an epigenetic mechanism via recruitment of a lysine-specific demethylase 1 (LSD1/KDM1A) to centromeres. This suppression results in defective de novo CENP-A loading at aging centromeres. By dual inhibition of p53 and LSD1/KDM1A in aged cells, we mitigate the reduction in centromeric proteins and centromeric transcripts, leading to the mitotic rejuvenation of these cells. These results offer insights into a unique mechanism for centromeric inactivation during aging and provide potential strategies to reactivate centromeres.
{"title":"Centromere inactivation during aging can be rescued in human cells","authors":"Sweta Sikder, Songjoon Baek, Truman McNeil, Yamini Dalal","doi":"10.1016/j.molcel.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.018","url":null,"abstract":"Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres in aged human fibroblasts and tissues and in various cellular senescent models. Our findings reveal that the centromeric histone H3 variant CENP-A is downregulated in aged cells in a p53-dependent manner. We observe repression of centromeric noncoding transcription through an epigenetic mechanism via recruitment of a lysine-specific demethylase 1 (LSD1/KDM1A) to centromeres. This suppression results in defective <em>de novo</em> CENP-A loading at aging centromeres. By dual inhibition of p53 and LSD1/KDM1A in aged cells, we mitigate the reduction in centromeric proteins and centromeric transcripts, leading to the mitotic rejuvenation of these cells. These results offer insights into a unique mechanism for centromeric inactivation during aging and provide potential strategies to reactivate centromeres.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"88 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.molcel.2024.12.016
Yoseop Yoon, Elodie Bournique, Lindsey V. Soles, Hong Yin, Hsu-Feng Chu, Christopher Yin, Yinyin Zhuang, Xiangyang Liu, Liang Liu, Joshua Jeong, Clinton Yu, Marielle Valdez, Lusong Tian, Lan Huang, Xiaoyu Shi, Georg Seelig, Fangyuan Ding, Liang Tong, Rémi Buisson, Yongsheng Shi
Pre-mRNA 3′ processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3′ processing in human cells. We show that the essential pre-mRNA 3′ processing factor retinoblastoma-binding protein 6 (RBBP6) associates strongly with NSs via its C-terminal intrinsically disordered region (IDR). Importantly, although the conserved N-terminal domain (NTD) of RBBP6 is sufficient for pre-mRNA 3′ processing in vitro, its IDR-mediated association with NSs is required for efficient pre-mRNA 3′ processing in cells. Through proximity labeling analyses, we provide evidence that pre-mRNA 3′ processing for over 50% of genes occurs near NSs. We propose that NSs serve as hubs for RNA polymerase II transcription, pre-mRNA splicing, and 3′ processing, thereby enhancing the efficiency and coordination of different gene expression steps.
{"title":"RBBP6 anchors pre-mRNA 3′ end processing to nuclear speckles for efficient gene expression","authors":"Yoseop Yoon, Elodie Bournique, Lindsey V. Soles, Hong Yin, Hsu-Feng Chu, Christopher Yin, Yinyin Zhuang, Xiangyang Liu, Liang Liu, Joshua Jeong, Clinton Yu, Marielle Valdez, Lusong Tian, Lan Huang, Xiaoyu Shi, Georg Seelig, Fangyuan Ding, Liang Tong, Rémi Buisson, Yongsheng Shi","doi":"10.1016/j.molcel.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.016","url":null,"abstract":"Pre-mRNA 3′ processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3′ processing in human cells. We show that the essential pre-mRNA 3′ processing factor retinoblastoma-binding protein 6 (RBBP6) associates strongly with NSs via its C-terminal intrinsically disordered region (IDR). Importantly, although the conserved N-terminal domain (NTD) of RBBP6 is sufficient for pre-mRNA 3′ processing <em>in vitro</em>, its IDR-mediated association with NSs is required for efficient pre-mRNA 3′ processing in cells. Through proximity labeling analyses, we provide evidence that pre-mRNA 3′ processing for over 50% of genes occurs near NSs. We propose that NSs serve as hubs for RNA polymerase II transcription, pre-mRNA splicing, and 3′ processing, thereby enhancing the efficiency and coordination of different gene expression steps.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"2 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-02DOI: 10.1016/j.molcel.2024.12.011
Alok Swaroop, Feng Yue
In this issue of Molecular Cell, Gambi, Boccalatte, Hernaez, et al.1 apply multiomics followed by genetic engineering to define then characterize epigenetic hubs that regulate processes crucial for T-ALL and use this insight to offer new avenues for therapeutic targeting.
{"title":"Chromatin hubs drive key regulatory networks in leukemia","authors":"Alok Swaroop, Feng Yue","doi":"10.1016/j.molcel.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.011","url":null,"abstract":"In this issue of <em>Molecular Cell</em>, Gambi, Boccalatte, Hernaez, et al.<span><span><sup>1</sup></span></span> apply multiomics followed by genetic engineering to define then characterize epigenetic hubs that regulate processes crucial for T-ALL and use this insight to offer new avenues for therapeutic targeting.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"51 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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