Akiko Nakayama, Masanori Nakayama, Christopher J. Turner, Susanne Höing, John J. Lepore, Ralf H. Adams
Genes & Development 27: 2576–2589 (2013)
基因与发育27:2576-2589 （2013）
{"title":"Corrigendum: Ephrin-B2 controls PDGFRβ internalization and signaling","authors":"Akiko Nakayama, Masanori Nakayama, Christopher J. Turner, Susanne Höing, John J. Lepore, Ralf H. Adams","doi":"10.1101/gad.353351.125","DOIUrl":"https://doi.org/10.1101/gad.353351.125","url":null,"abstract":"<strong>Genes & Development 27:</strong> 2576–2589 (2013)","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"55 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145434082","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}
Precise intercellular communication is critical for cellular decision-making. The segmentation clock is an oscillatory gene network regulating periodic segmentation of the presomitic mesoderm (PSM) in vertebrate embryos. Oscillations between neighboring cells are thought to be coupled by DELTA–NOTCH signaling. To directly test this experimentally, Isomura and colleagues (doi:10.1101/gad.352538.124) reconstituted this coupling using synthetic biology. They integrated a synthetic DELTA–NOTCH pathway into DELTA-deficient PSM organoids, which restored cell–cell communication. Additionally, optogenetic activation of the synthetic ligand further revealed that the dynamics of ligand presentation are crucial for effective communication. This work directly demonstrates the importance of oscillatory cell–cell signaling in development and provides a blueprint for using synthetic circuits in future studies.
{"title":"Rewiring gene circuits to dissect oscillatory signaling dynamics","authors":"Marek J. van Oostrom, Katharina F. Sonnen","doi":"10.1101/gad.353319.125","DOIUrl":"https://doi.org/10.1101/gad.353319.125","url":null,"abstract":"Precise intercellular communication is critical for cellular decision-making. The segmentation clock is an oscillatory gene network regulating periodic segmentation of the presomitic mesoderm (PSM) in vertebrate embryos. Oscillations between neighboring cells are thought to be coupled by DELTA–NOTCH signaling. To directly test this experimentally, Isomura and colleagues (doi:10.1101/gad.352538.124) reconstituted this coupling using synthetic biology. They integrated a synthetic DELTA–NOTCH pathway into DELTA-deficient PSM organoids, which restored cell–cell communication. Additionally, optogenetic activation of the synthetic ligand further revealed that the dynamics of ligand presentation are crucial for effective communication. This work directly demonstrates the importance of oscillatory cell–cell signaling in development and provides a blueprint for using synthetic circuits in future studies.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"1 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397610","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}
Adebanjo Adedoja, Niclole Stuhr, Yifei Zhou, Yuyao Zhang, Armen Yerevanian, Alexander A. Soukas
Mitochondria play a crucial role in cellular energy metabolism and homeostasis and are strongly implicated in aging and age-related diseases. The outer mitochondrial membrane protein voltage-dependent anion channel (VDAC) plays multiple roles in mitochondrial homeostasis, including transport of metabolites, ATP, and Ca2+. Dysregulation of VDAC levels has been associated with cancer, neurodegeneration, metabolic disorders, and aging. Previously, we demonstrated that elevated VDAC-1 levels in Caenorhabditis elegans lead to increased mitochondrial permeability and reduced life span. Here we demonstrate that reduced VDAC-1 function extends life span through the activation of the mitochondrial unfolded protein response (UPRmt), a conserved stress response that maintains mitochondrial proteostasis and is linked to life span extension in multiple species. Leveraging unbiased genomic discovery, we identified genes encoding several proteins in the PeBoW complex as a critical mediator of UPRmt activation following VDAC-1 loss. More broadly, we demonstrated a universal requirement for several PeBoW component genes across diverse mitochondrial stressors in order to fully animate the UPRmt. Our findings reveal a heretofore unappreciated role for PeBoW components in UPRmt induction and life span extension in response to mitochondrial stress, highlighting its essential function in mitochondrial quality control and longevity pathways.
{"title":"Longevity-promoting mitochondrial unfolded protein response activation requires elements of the PeBoW complex","authors":"Adebanjo Adedoja, Niclole Stuhr, Yifei Zhou, Yuyao Zhang, Armen Yerevanian, Alexander A. Soukas","doi":"10.1101/gad.352979.125","DOIUrl":"https://doi.org/10.1101/gad.352979.125","url":null,"abstract":"Mitochondria play a crucial role in cellular energy metabolism and homeostasis and are strongly implicated in aging and age-related diseases. The outer mitochondrial membrane protein voltage-dependent anion channel (VDAC) plays multiple roles in mitochondrial homeostasis, including transport of metabolites, ATP, and Ca<sup>2+</sup>. Dysregulation of VDAC levels has been associated with cancer, neurodegeneration, metabolic disorders, and aging. Previously, we demonstrated that elevated VDAC-1 levels in <em>Caenorhabditis elegans</em> lead to increased mitochondrial permeability and reduced life span. Here we demonstrate that reduced VDAC-1 function extends life span through the activation of the mitochondrial unfolded protein response (UPR<sup>mt</sup>), a conserved stress response that maintains mitochondrial proteostasis and is linked to life span extension in multiple species. Leveraging unbiased genomic discovery, we identified genes encoding several proteins in the PeBoW complex as a critical mediator of UPR<sup>mt</sup> activation following VDAC-1 loss. More broadly, we demonstrated a universal requirement for several PeBoW component genes across diverse mitochondrial stressors in order to fully animate the UPR<sup>mt</sup>. Our findings reveal a heretofore unappreciated role for PeBoW components in UPR<sup>mt</sup> induction and life span extension in response to mitochondrial stress, highlighting its essential function in mitochondrial quality control and longevity pathways.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"171 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397613","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}
Ting Li, Catherine R. Dufour, Lingwei Han, Anthony Alfonso, Mirna Farhat, Annabelle Beaumier, Qian Chen, Jin-jian Lu, Vincent Giguère
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). The molecular mechanisms underlying the progression of CRPC toward NEPC remain incompletely understood, and effective treatments remain to be discovered. Here, we report that loss of the nuclear receptor ERRγ promotes neuroendocrine differentiation in a Pten-deficient mouse model of prostate adenocarcinoma. These findings were recapitulated in advanced cellular and xenograft models of human prostate cancer. Critically, we show that ERRγ gain of function can reverse instilled NEPC features accompanied by suppression of growth and oncogenic metabolic reprogramming. Activation of a neuroendocrine transcriptional program enabled by ERRγ deficiency unveiled a targetable vulnerability exploited by the combined pharmacological inhibition of EZH2 and RET kinase that effectively inhibited the growth of ERRγ-deficient tumor organoids and cells. Collectively, our findings demonstrate that ERRγ downregulation facilitates prostate cancer adeno-to-neuroendocrine transformation and offer potential therapeutic strategies to prevent/treat the development of poor outcome NEPC.
{"title":"ERRγ impedes neuroendocrine prostate cancer development","authors":"Ting Li, Catherine R. Dufour, Lingwei Han, Anthony Alfonso, Mirna Farhat, Annabelle Beaumier, Qian Chen, Jin-jian Lu, Vincent Giguère","doi":"10.1101/gad.353024.125","DOIUrl":"https://doi.org/10.1101/gad.353024.125","url":null,"abstract":"Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). The molecular mechanisms underlying the progression of CRPC toward NEPC remain incompletely understood, and effective treatments remain to be discovered. Here, we report that loss of the nuclear receptor ERRγ promotes neuroendocrine differentiation in a Pten-deficient mouse model of prostate adenocarcinoma. These findings were recapitulated in advanced cellular and xenograft models of human prostate cancer. Critically, we show that ERRγ gain of function can reverse instilled NEPC features accompanied by suppression of growth and oncogenic metabolic reprogramming. Activation of a neuroendocrine transcriptional program enabled by ERRγ deficiency unveiled a targetable vulnerability exploited by the combined pharmacological inhibition of EZH2 and RET kinase that effectively inhibited the growth of ERRγ-deficient tumor organoids and cells. Collectively, our findings demonstrate that ERRγ downregulation facilitates prostate cancer adeno-to-neuroendocrine transformation and offer potential therapeutic strategies to prevent/treat the development of poor outcome NEPC.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"22 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397586","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}
Lei Ji, Chue Vin Chin, Gangyu Sun, Olga Charlats, Chad Vickers, Bo Lu, Frederic Sigoillot, Zhizhi Wang, Wenqing Xu, Feng Cong
Stabilization of β-catenin on the dorsal side of the embryo is critical for the formation of the dorsal organizer. The novel transmembrane protein Huluwa (Hwa) has recently been identified as the maternal dorsal determinant responsible for β-catenin stabilization in dorsal organizer formation. The molecular mechanism by which Hwa induces WNT-independent β-catenin stabilization remains elusive. In this study, we demonstrate that the conserved PPNSP motif of Hwa is phosphorylated by GSK3 and that the phosphorylated PPNSP motif potently inhibits GSK3, leading to β-catenin stabilization. Notably, the phosphorylated PPNSP motif of Hwa has stronger GSK3 inhibitory activity than the phosphorylated PPPSP motif of LRP6. Molecular dynamics simulations suggest that the PPNpSP peptide has stronger affinity for GSK3 than the PPPpSP peptide, facilitated by the hydrogen bonding capacity of the asparagine residue. Consistent with Hwa's GSK3 inhibitory activity, Hwa enhances SIAH1-dependent degradation of AXIN. Hwa-induced β-catenin stabilization and AXIN degradation are significantly enhanced by oligomerization. Thus, Hwa stabilizes β-catenin through a molecular mechanism similar to that of LRP6 in mediating WNT signaling, representing a striking example of molecular convergence.
{"title":"Dorsal determinant Hwa stabilizes β-catenin through direct inhibition of GSK3","authors":"Lei Ji, Chue Vin Chin, Gangyu Sun, Olga Charlats, Chad Vickers, Bo Lu, Frederic Sigoillot, Zhizhi Wang, Wenqing Xu, Feng Cong","doi":"10.1101/gad.352622.125","DOIUrl":"https://doi.org/10.1101/gad.352622.125","url":null,"abstract":"Stabilization of β-catenin on the dorsal side of the embryo is critical for the formation of the dorsal organizer. The novel transmembrane protein Huluwa (Hwa) has recently been identified as the maternal dorsal determinant responsible for β-catenin stabilization in dorsal organizer formation. The molecular mechanism by which Hwa induces WNT-independent β-catenin stabilization remains elusive. In this study, we demonstrate that the conserved PPNSP motif of Hwa is phosphorylated by GSK3 and that the phosphorylated PPNSP motif potently inhibits GSK3, leading to β-catenin stabilization. Notably, the phosphorylated PPNSP motif of Hwa has stronger GSK3 inhibitory activity than the phosphorylated PPPSP motif of LRP6. Molecular dynamics simulations suggest that the PPNpSP peptide has stronger affinity for GSK3 than the PPPpSP peptide, facilitated by the hydrogen bonding capacity of the asparagine residue. Consistent with Hwa's GSK3 inhibitory activity, Hwa enhances SIAH1-dependent degradation of AXIN. Hwa-induced β-catenin stabilization and AXIN degradation are significantly enhanced by oligomerization. Thus, Hwa stabilizes β-catenin through a molecular mechanism similar to that of LRP6 in mediating WNT signaling, representing a striking example of molecular convergence.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"213 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246531","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}
Jacques Bonnet, Eva Triantopoulou, Jasmin Birnhäupl, Chenggang Lu, Margaret T. Fuller, Jürg Müller
Polycomb chromatin domains are chromosomal regions decorated with histone H2A monoubiquitination at lysine 119 (H2Aub1) and histone H3 trimethylation at lysine 27 (H3K27me3). These domains are dynamically shaped through the actions of different Polycomb group protein complexes to control gene expression during development. To assess how different Polycomb group subcomplexes contribute to these histone modification profiles in Drosophila embryos, we used mutants that abrogate their function. Canonical Polycomb repressive complex (PRC) 1 deposits low levels of H2Aub1 solely at Polycomb target genes, whereas variant PRC1 generates the bulk of H2Aub1 genome-wide. In late-stage embryos, PR-DUB-mediated deubiquitination effectuates a uniform low-level H2Aub1 profile across the genome. The combined activities of PRC2.1 and PRC2.2 drive the formation and maintenance of most H3K27me3 domains, but PRC2.1 is the limiting enzyme for creating such domains at HOX genes. Surprisingly, reduction in the H3K27me3 level and repression defects caused by removing PRC2.1 were largely rescued in animals also lacking PR-DUB, which showed extensive H2Aub1 accumulation at Polycomb targets that promoted compensatory H3K27me3 deposition by PRC2.2. Diversification of Polycomb protein complexes combined with feedback loop mechanisms involving histone modification cross-talk equips the system with the plasticity, adaptability, and buffering capacity needed to safeguard cell fate decisions during development.
{"title":"Histone modification cross-talk and protein complex diversification confer plasticity to Polycomb repression","authors":"Jacques Bonnet, Eva Triantopoulou, Jasmin Birnhäupl, Chenggang Lu, Margaret T. Fuller, Jürg Müller","doi":"10.1101/gad.353148.125","DOIUrl":"https://doi.org/10.1101/gad.353148.125","url":null,"abstract":"Polycomb chromatin domains are chromosomal regions decorated with histone H2A monoubiquitination at lysine 119 (H2Aub1) and histone H3 trimethylation at lysine 27 (H3K27me3). These domains are dynamically shaped through the actions of different Polycomb group protein complexes to control gene expression during development. To assess how different Polycomb group subcomplexes contribute to these histone modification profiles in <em>Drosophila</em> embryos, we used mutants that abrogate their function. Canonical Polycomb repressive complex (PRC) 1 deposits low levels of H2Aub1 solely at Polycomb target genes, whereas variant PRC1 generates the bulk of H2Aub1 genome-wide. In late-stage embryos, PR-DUB-mediated deubiquitination effectuates a uniform low-level H2Aub1 profile across the genome. The combined activities of PRC2.1 and PRC2.2 drive the formation and maintenance of most H3K27me3 domains, but PRC2.1 is the limiting enzyme for creating such domains at HOX genes. Surprisingly, reduction in the H3K27me3 level and repression defects caused by removing PRC2.1 were largely rescued in animals also lacking PR-DUB, which showed extensive H2Aub1 accumulation at Polycomb targets that promoted compensatory H3K27me3 deposition by PRC2.2. Diversification of Polycomb protein complexes combined with feedback loop mechanisms involving histone modification cross-talk equips the system with the plasticity, adaptability, and buffering capacity needed to safeguard cell fate decisions during development.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"18 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246532","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}
Yanhong Zhang, Yingjuan Qian, Jin Zhang, Wensheng Yan, Yong-Sam Jung, Mingyi Chen, Eric Huang, Kent Lloyd, Yuyou Duan, Jian Wang, Gang Liu, Xinbin Chen
Genes & Development 31: 1243–1256 (2017)
基因与发育31:1243-1256 （2017）
{"title":"Corrigendum: Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2","authors":"Yanhong Zhang, Yingjuan Qian, Jin Zhang, Wensheng Yan, Yong-Sam Jung, Mingyi Chen, Eric Huang, Kent Lloyd, Yuyou Duan, Jian Wang, Gang Liu, Xinbin Chen","doi":"10.1101/gad.353221.125","DOIUrl":"https://doi.org/10.1101/gad.353221.125","url":null,"abstract":"<strong>Genes & Development 31:</strong> 1243–1256 (2017)","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"35 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195151","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}
Bing Yang, Brian J. Galletta, Rima M. Sakhawala, Nasser M. Rusan, Katherine McJunkin
Precise control of miRNA biogenesis is of extreme importance, because misregulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first cleavage step in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the N-terminal region of DROSHA is less characterized due to its high intrinsic disorder. Here we demonstrate that Microprocessor forms condensates with properties consistent with liquid–liquid phase separation (LLPS) in select tissues in Caenorhabditis elegans. Although DRSH-1/Drosha recruitment to granules is only partially dependent on its intrinsically disordered regions (IDRs), one of these N-terminal IDRs is crucial for biogenesis of a subset of miRNAs and normal development. A cis region of IDR-dependent miRNAs confers IDR dependence to another miRNA, suggesting that the IDR recognizes sequences or structures in the miRNA primary transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates.
{"title":"An intrinsically disordered region of Drosha selectively promotes miRNA biogenesis independent of tissue-specific Microprocessor condensates","authors":"Bing Yang, Brian J. Galletta, Rima M. Sakhawala, Nasser M. Rusan, Katherine McJunkin","doi":"10.1101/gad.352815.125","DOIUrl":"https://doi.org/10.1101/gad.352815.125","url":null,"abstract":"Precise control of miRNA biogenesis is of extreme importance, because misregulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first cleavage step in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the N-terminal region of DROSHA is less characterized due to its high intrinsic disorder. Here we demonstrate that Microprocessor forms condensates with properties consistent with liquid–liquid phase separation (LLPS) in select tissues in <em>Caenorhabditis elegans</em>. Although DRSH-1/Drosha recruitment to granules is only partially dependent on its intrinsically disordered regions (IDRs), one of these N-terminal IDRs is crucial for biogenesis of a subset of miRNAs and normal development. A <em>cis</em> region of IDR-dependent miRNAs confers IDR dependence to another miRNA, suggesting that the IDR recognizes sequences or structures in the miRNA primary transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"45 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188777","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}
Heart formation depends on the finely tuned activity of transcriptional regulators, yet the networks they control are only now being defined. In this issue of Genes & Development, Muncie-Vasik and colleagues (doi:10.1101/gad.352889.125) analyzed the role of MEF2C, which is a key driver of heart formation. By characterizing MEF2C's temporal effects on mRNA profiles and chromatin structure, the investigators computationally reconstructed downstream gene regulatory networks, which turned out to be remarkably specific for the different heart tube segments that form the inflow tract, chambers, and outflow tract. The results comprise an extremely fine-grained view of the network logic of heart formation.
{"title":"MEF2C networks in heart tube development","authors":"Hassan Abdulrazzak, Mark Mercola","doi":"10.1101/gad.353315.125","DOIUrl":"https://doi.org/10.1101/gad.353315.125","url":null,"abstract":"Heart formation depends on the finely tuned activity of transcriptional regulators, yet the networks they control are only now being defined. In this issue of <em>Genes & Development</em>, Muncie-Vasik and colleagues (doi:10.1101/gad.352889.125) analyzed the role of MEF2C, which is a key driver of heart formation. By characterizing MEF2C's temporal effects on mRNA profiles and chromatin structure, the investigators computationally reconstructed downstream gene regulatory networks, which turned out to be remarkably specific for the different heart tube segments that form the inflow tract, chambers, and outflow tract. The results comprise an extremely fine-grained view of the network logic of heart formation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"57 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141387","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}
MyoD is well known for its ability to reprogram a broad range of cell types into myogenic cells and for its pioneer function in activating the myogenic program during muscle development and regeneration. The basic helix–loop–helix (bHLH) protein achieves this by directly binding to E-boxes in DNA and recruiting proteins like histone acetyltransferases and the SWI/SNF chromatin remodeling complex. Interestingly, Nicoletti and colleagues (doi:10.1101/gad.352708.125) report in this issue of Genes & Development an unexpected finding; namely, that MyoD can also act as a repressor. This repressive activity is E-box-independent, meaning that MyoD can be indirectly recruited to distinct sites in chromatin. Transcription factor motifs enriched at these sites correspond to E2F, NF-Y, and Jun/Fos motifs. The genes that are repressed by this noncanonical MyoD function control nonmyogenic fates and participate in cell cycle regulation as well as proliferation. At such sites, MyoD binding is associated with chromatin compaction and repression of transcription.
{"title":"The two faces of MyoD: repressor and activator of gene expression during myogenesis","authors":"Carmen Birchmeier","doi":"10.1101/gad.353232.125","DOIUrl":"https://doi.org/10.1101/gad.353232.125","url":null,"abstract":"MyoD is well known for its ability to reprogram a broad range of cell types into myogenic cells and for its pioneer function in activating the myogenic program during muscle development and regeneration. The basic helix–loop–helix (bHLH) protein achieves this by directly binding to E-boxes in DNA and recruiting proteins like histone acetyltransferases and the SWI/SNF chromatin remodeling complex. Interestingly, Nicoletti and colleagues (doi:10.1101/gad.352708.125) report in this issue of <em>Genes & Development</em> an unexpected finding; namely, that MyoD can also act as a repressor. This repressive activity is E-box-independent, meaning that MyoD can be indirectly recruited to distinct sites in chromatin. Transcription factor motifs enriched at these sites correspond to E2F, NF-Y, and Jun/Fos motifs. The genes that are repressed by this noncanonical MyoD function control nonmyogenic fates and participate in cell cycle regulation as well as proliferation. At such sites, MyoD binding is associated with chromatin compaction and repression of transcription.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"8 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116506","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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