GENES & DEVELOPMENT基因与发育
GENES & DEVELOPMENT(英文缩写 GENE DEV),ISSN 0890-9369,eISSN 1549-5477,中文译名:基因与发育 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-28 至 2026-09-28，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 12.890 | Q1 |
| 2022 | 10.500 | Q1 |
| 2023 | 7.500 | Q1 |
| 2024 | 7.700 | Q1 |
| 2025 | 7.400 | Q1 |
GENES & DEVELOPMENT 最新收录文献
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1. Initial perturbations triggered by p53 loss in stem cells.
PMID:日期:2026-09-22p53 is frequently mutated in human cancers, but how it normally acts to prevent transformation is not fully understood. The initial events triggered by p53 loss are commonly extrapolated from cell lines, patient tumors, or mouse models in which p53 has been absent for long durations (e.g., months, years). In these contexts, collateral changes, competitive selection, and secondary adaptations may obscure the immediate impact of p53 elimination. Therefore, to inspect the direct consequences triggered by p53 loss in real time, we developed a platform that enables conditional removal of p53 in unstressed mouse embryonic stem cells. Within 48 h, activated germline programs were accompanied by altered chromatin profiles and downregulated canonical p53 targets. At the single-cell level, extensive heterogeneity was observed in the form of erupting retroelements, increased SINE accessibility, features of Warburg metabolism, and functional germ cell effectors (e.g., and ). Together, these findings expose ground state functions for p53 and establish that germline transitions, activated mobile elements, and metabolic reprogramming define acute perturbations caused by p53 loss.
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2. {"_":"Genomic imprinting of the metabolic regulator gene is regulated by a paternal sub-TAD anchored at .","i":["Klf14","Mest"]}
PMID:日期:2026-09-21KLF14 acts as a master regulator of gene expression in adipose tissue and variants at the human gene show reproducible association with type 2 diabetes and metabolic syndrome. Risk alleles are only pathological when maternally inherited, consistent with the observation that is a maternally expressed imprinted gene in human and mouse. However, how genomic imprinting is regulated at this important locus is currently unknown. In both species, is located ∼200 kb away from the paternally expressed imprinted gene , regulated by a maternal gametic differentially methylated region (gDMR) at its promoter. Although the promoter is unmethylated in most tissues, maternally inherited DNA methylation marks are paradoxically required for expression. Here, we show that and reside within the same topologically associating domain (TAD) in embryonic stem cells (ESCs), defined by biallelic CTCF binding at the boundaries. Using allele-specific 4C-seq, we show that CTCF binding to the unmethylated gDMR generates a paternal allele-specific sub-TAD encompassing CRISPR-Cas9 deletions of the paternal promoter region in ESCs and in vivo in mutant mice result in loss of expression and acquisition of biallelic expression at By analyzing epigenetic marks and chromatin looping in -expressing pituitary cells, we identify a putative enhancer element shared by and , providing a mechanistic model for the regulation of imprinting. This work defines a new role for the maternally methylated gDMR, revealing that it exerts long-range effects via allele-specific modulation of TAD structures and acts as an imprinting control region in the regulation of imprinting.
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3. {"_":" Scm self-assembles into PcG bodies to recruit PRC2.1 to target genes during Polycomb silencing initiation.","i":["Drosophila"]}
PMID:日期:2026-09-21While Polycomb-based gene silencing relies upon the generation of large, condensed domains of histone H3K27 trimethylation, the mechanisms forming and maintaining these domains are incompletely understood. Several previously identified mechanisms concentrate PRC2 and its H3K27me3 activity, including allosteric activation, binding to H2Aub, and concentration into PcG bodies through weak multivalent interactions with other Polycomb group proteins. Here, using the nurse cell system to study silencing initiation in developing tissue, we discover a new mechanism. The scaffolding protein Sex comb on midleg (Scm) first polymerizes into PcG bodies independently of PRC1 and PRC2. These Scm-containing bodies then recruit PRC2 through a direct, structured interaction between the Scm-Zf-FCS domain and the Pcl atypical Tudor domain. Finally, we show that the Scm-Zf-FCS/Pcl-Tudor interaction is required for viability and Hox gene regulation during somatic cell development. Our work discovers a new mechanism anchoring PRC2 to PcG bodies that explains how cells can rapidly create and maintain large domains of H3K27me3. It also raises a new possibility that cells could regulate Scm polymerization to determine the size and location of H3K27me3 domains.
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4. The hnRNPA1 D262V amyotrophic lateral sclerosis (ALS) mutation is linked to mitochondrial dysfunction.
PMID:日期:2026-09-15Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by motor neuron loss and has been genetically linked to mutations in RNA-binding proteins. A mutation D262V in the RNA-binding protein hnRNPA1, found in a subset of ALS patients, causes widespread splicing pattern changes. Cells expressing this hnRNPA1 mutation exhibit aggregation, reduced proliferation, altered stress granules and abnormal neuronal growth. To further elucidate how a single amino acid substitution in a splicing factor might impact cell growth, we employed ribosome profiling to study translational dynamics across the transcriptome in hnRNPA1 mutant cells. Differential ribosome occupancy was observed for a small number of transcripts linked to synaptic organization and GTPase functions, as well as disrupted codon usage and a global stalling of translation. This downregulation of translation coincided with suppression of the mTOR/AKT signaling pathway. RNA splicing changes in transcripts from genes linked to cilia/cell projections, GTPase cycles and glutamate signaling were also observed. Importantly, major mitochondrial dysfunction and mitochondrial fragmentation were found in hnRNPA1 D262V mutant cells. Overall, this study demonstrates how a single amino acid change in an RNA binding protein can contribute to disrupting cell growth and mitochondrial function related to defects linked to neuronal death in ALS.
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5. Sharp cell type boundaries emerge from coordinated morphogen signaling.
PMID:日期:2026-09-10Classic models of the French flag problem depict sharp cell type boundaries emerging from threshold responses to morphogen gradients. How discrete cell type boundaries arise from morphogen signals that vary continuously across developing tissues remains incompletely understood. We use hair follicle dermal condensate (DC) formation to study a sharp developmental transition in which proliferative progenitors undergo cell cycle exit concurrent with molecular differentiation. Using genetic and genomic approaches, we show that Wnt and Hedgehog signaling coordinate separable cellular events during DC commitment. Elevated Wnt signaling promotes cell cycle exit through reduced chromatin binding of the Hedgehog mediator GLI3, while Hedgehog signaling induces differentiation genes in a Wnt-dependent manner and simultaneously elevates Wnt activity. When these responses coincide, differentiation and cell cycle exit occur together, limiting the duration and abundance of intermediate states and producing a sharp boundary. When they do not, intermediate states persist and expand, producing a graded boundary. Thus, a sharp boundary can emerge from a continuous transition that is compressed in time and space.
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6. Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.
PMID:日期:2026-09-10Alkylation chemotherapy is commonly used against tumors such as glioblastoma, yet resistance often develops through downregulation of mismatch repair (MMR). Previous work has established that loss of MMR prevents the excision of the thymine-containing strand across meG-T mismatches, thereby avoiding the futile repair cycle that ultimately leads to cell death. Here, we provide an alternative explanation to this prevailing mechanism of chemoresistance by MMR loss. We found that the MMR protein MutLα physically and functionally interacts with the base excision repair (BER) enzyme methylpurine DNA glycosylase (MPG), which processes common alkylation adducts, such as 7meG and 3meA. Biochemical reconstitution demonstrates that MutLα activates MPG glycosylase activity by promoting MPG substrate binding, and enhancing MPG release from the abasic site product, thereby facilitating enzyme turnover. This glycosylase stimulation requires ATP hydrolysis as well as the MLH1-interacting region on MPG. Both MutLα or its ability to interact with MPG promote the generation of alkylation-induced abasic sites in cells, which contribute to the cytotoxicity of methyl methanesulfonate (MMS), an S2 alkylating agent that does not produce meG. Our results provide new insight into the mechanism of alkylation chemoresistance and uncover an unappreciated cross-talk between MMR and BER.
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7. A HUWE1 regulatory helix gates ASCL1 degradation through its C-terminal phospho-degron in small cell lung cancer.
PMID:日期:2026-09-10Lineage-defining transcription factors are key oncogenic drivers but remain difficult to target pharmacologically due to the absence of ligandable pockets. The molecular rules governing substrate recognition by large HECT ubiquitin ligases also remain incompletely understood, limiting efforts to exploit these enzymes for targeted protein degradation. Here we combine genome-wide CRISPR knockout screening with base editor tiling screens at amino acid resolution, both coupled to an endogenous knock-in reporter of the SCLC lineage oncogenic transcription factor ASCL1, to systematically interrogate the mechanisms governing its degradation. These complementary screens unbiasedly identify the HECT ubiquitin ligase HUWE1 as the dominant regulator of ASCL1 stability in small cell lung cancer (SCLC) and resolve a conserved C-terminal phospho-degron centered on Ser207 and terminal Trp/Phe residues that are required for HUWE1 docking and ubiquitin-mediated degradation. Unexpectedly, base editor screening further uncovers a previously unrecognized regulatory module within HUWE1: a short negatively charged helix that functions as an autoinhibitory gate controlling access of phospho-degron substrates to HUWE1. Charge-flipping mutations within this regulatory helix relieve autoinhibition and accelerate degradation of multiple HUWE1 phospho-degron substrates, including ASCL1 and the canonical HUWE1 substrate DDIT4. Stabilization of ASCL1 through degron disruption paradoxically impairs SCLC proliferation, revealing that dynamic proteasome-coupled turnover is required for transcription factor function. Together, these findings reveal molecular rules governing HUWE1 phospho-degron recognition and identify a regulatory gate controlling substrate engagement. They also illustrate a generalizable strategy for resolving degradation mechanisms of undruggable transcription factors in their endogenous cellular context.
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8. Regulatory circuits that build and sustain noninfectious granulomas.
PMID:日期:2026-09-10Noninfectious granulomas organize immune cells into persistent tissue aggregates without an identifiable pathogen. Across diverse diseases, inflammation that should resolve instead persists, producing hallmark pathologic changes in tissue architecture that compromise organ function. Here, we synthesize recent studies to move beyond linear cytokine models and propose that granulomas persist through regulatory circuits linking immune cells, metabolism, and stroma. Maintenance reflects reinforcement among these local programs rather than a single inflammatory pathway. Comparisons across granulomatous diseases, including sarcoidosis, can distinguish disease-specific wiring from conserved maintenance programs. Defining these programs should identify strategies to dismantle established lesions.
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9. Dangerous liaisons: interactions between cancer cells and adipocytes as drivers of cancer progression.
PMID:日期:2026-09-09Metabolic plasticity and flexibility are key characteristics that allow cancer cells to adapt and thrive in different environments. Specifically, cancer cells can dynamically change the routing of metabolic pathways in response to environmental changes and adapt their metabolic activity depending on local nutrient availability. The tumor microenvironment (TME) plays crucial roles in cancer development and progression. It is now widely accepted that different stromal cells, as well as soluble factors, including metabolites, derived from the TME support cancer cell proliferation and survival and drive migration, invasion, and the formation of metastases. Some cancer types grow in the proximity of adipose tissue (AT), which is mostly composed of mature adipocytes, a specialized cell type responsible for the storage and controlled release of lipids. In response to specific stimuli released by cancer cells, adipocytes can transform into cancer-associated adipocytes (CAAs). CAAs release signaling molecules, and provide fatty acids to cancer cells and other cell types in the TME, which can then utilize these fatty acids as fuel. The interaction between cancer cells and adipocytes creates a dynamic cross-talk that promotes disease progression through multiple mechanisms. In this review, we aim to provide an overview of the main factors in the CAA-cancer cell cross-talk, with a focus on the metabolic consequences of this interaction.
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10. Tales of destruction and repair: the changing view of MYC proteins in tumorigenesis.
PMID:日期:2026-09-09MYC proteins are classically viewed as oncoproteins because they act as DNA-bound transcription factors that drive characteristic gene expression programs. Building on this view, recent work has shown that MYC proteins engage in multiple protein complexes that resolve transcription-associated stress and that they function as both DNA- and RNA-binding proteins. These findings suggest that, through these activities, MYC proteins enhance the stress resilience of proliferating cells and enable tumor cells to sustain nonphysiological, oncogenic gene expression programs.