Genes & development最新文献_第3页

NEAT1 promotes genome stability via m⁶A methylation-dependent regulation of CHD4. NEAT1 通过 m6A 甲基化依赖性调控 CHD4 促进基因组稳定性。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.351913.124

Victoria Mamontova, Barbara Trifault, Anne-Sophie Gribling-Burrer, Patrick Bohn, Lea Boten, Pit Preckwinkel, Peter Gallant, Daniel Solvie, Carsten P Ade, Dimitrios Papadopoulos, Martin Eilers, Tony Gutschner, Redmond P Smyth, Kaspar Burger

{"title":"NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4.","authors":"Victoria Mamontova, Barbara Trifault, Anne-Sophie Gribling-Burrer, Patrick Bohn, Lea Boten, Pit Preckwinkel, Peter Gallant, Daniel Solvie, Carsten P Ade, Dimitrios Papadopoulos, Martin Eilers, Tony Gutschner, Redmond P Smyth, Kaspar Burger","doi":"10.1101/gad.351913.124","DOIUrl":"10.1101/gad.351913.124","url":null,"abstract":"Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear. Here, we investigate the expression, modification, localization, and structure of NEAT1 in response to DNA double-strand breaks (DSBs). DNA damage increases the levels and N6-methyladenosine (m6A) marks on NEAT1, which promotes alterations in NEAT1 structure, accumulation of hypermethylated NEAT1 at promoter-associated DSBs, and DSB signaling. The depletion of NEAT1 impairs DSB focus formation and elevates DNA damage. The genome-protective role of NEAT1 is mediated by the RNA methyltransferase 3 (METTL3) and involves the release of the chromodomain helicase DNA binding protein 4 (CHD4) from NEAT1 to fine-tune histone acetylation at DSBs. Our data suggest a direct role for NEAT1 in DDR.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"915-930"},"PeriodicalIF":7.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Temperature matters: the potential impact of thermoregulatory mechanisms in brain-body physiology. 温度问题：体温调节机制对脑-体生理学的潜在影响。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.352294.124

Elizabeth A Repasky, Bonnie L Hylander, Hemn Mohammadpour

引用次数: 0

Interoceptive inference and prediction in food-related disorders. 食物相关疾病的感知推理和预测。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.352301.124

Madhav Subramanian, Christoph A Thaiss

引用次数: 0

Deciphering visceral instincts: a scientific quest to unravel food choices from molecules to mind. 解密内脏本能：从分子到思维，揭示食物选择的科学探索。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.352279.124

Emily Alway, Naama Reicher, Diego V Bohórquez

引用次数: 0

Decoding biology with massively parallel reporter assays and machine learning. 利用大规模并行报告测定和机器学习解码生物学。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.351800.124

Alyssa La Fleur, Yongsheng Shi, Georg Seelig

引用次数: 0

A germline PAF1 paralog complex ensures cell type-specific gene expression 种系 PAF1 旁系复合物确保细胞类型特异性基因表达

IF 10.5 1区生物学

Genes & development Pub Date : 2024-09-27 DOI: 10.1101/gad.351930.124

Astrid Pold Vilstrup, Archica Gupta, Anna Jon Rasmussen, Anja Ebert, Sebastian Riedelbauch, Marie Vestergaard Lukassen, Rippei Hayashi, Peter Andersen

{"title":"A germline PAF1 paralog complex ensures cell type-specific gene expression","authors":"Astrid Pold Vilstrup, Archica Gupta, Anna Jon Rasmussen, Anja Ebert, Sebastian Riedelbauch, Marie Vestergaard Lukassen, Rippei Hayashi, Peter Andersen","doi":"10.1101/gad.351930.124","DOIUrl":"https://doi.org/10.1101/gad.351930.124","url":null,"abstract":"Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"22 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328633","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}

引用次数: 0

The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma. 多发性骨髓瘤中 MAF 和 MYC 致癌基因表达程序的维持需要 SAGA 乙酰转移酶模块。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-09-19 DOI: 10.1101/gad.351789.124

Ying-Jiun C Chen, Govinal Badiger Bhaskara, Yue Lu, Kevin Lin, Sharon Y R Dent

{"title":"The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma.","authors":"Ying-Jiun C Chen, Govinal Badiger Bhaskara, Yue Lu, Kevin Lin, Sharon Y R Dent","doi":"10.1101/gad.351789.124","DOIUrl":"10.1101/gad.351789.124","url":null,"abstract":"Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of data sets in the Cancer Dependency Map Project revealed that many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), and cleavage under targets and release using nuclease assay (CUT&RUN) results identified pathways directly regulated by ADA2B including MTORC1 signaling and oncogenic programs driven by MYC, E2F, and MM-specific MAF. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found that the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"738-754"},"PeriodicalIF":7.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 RNA for neurological and neuromuscular disease. 针对神经和神经肌肉疾病的 RNA 治疗。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-09-19 DOI: 10.1101/gad.351612.124

Jodi L Bubenik, Marina M Scotti, Maurice S Swanson

引用次数: 0

TFEB controls expression of human syncytins during cell-cell fusion. TFEB 在细胞-细胞融合过程中控制人类合胞素的表达。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-09-19 DOI: 10.1101/gad.351633.124

Meagan N Esbin, Liza Dahal, Vinson B Fan, Joey McKenna, Eric Yin, Xavier Darzacq, Robert Tjian

{"title":"TFEB controls expression of human syncytins during cell-cell fusion.","authors":"Meagan N Esbin, Liza Dahal, Vinson B Fan, Joey McKenna, Eric Yin, Xavier Darzacq, Robert Tjian","doi":"10.1101/gad.351633.124","DOIUrl":"10.1101/gad.351633.124","url":null,"abstract":"During human development, a temporary organ is formed, the placenta, which invades the uterine wall to support nutrient, oxygen, and waste exchange between the mother and fetus until birth. Most of the human placenta is formed by a syncytial villous structure lined by syncytialized trophoblasts, a specialized cell type that forms via cell-cell fusion of underlying progenitor cells. Genetic and functional studies have characterized the membrane protein fusogens Syncytin-1 and Syncytin-2, both of which are necessary and sufficient for human trophoblast cell-cell fusion. However, identification and characterization of upstream transcriptional regulators regulating their expression have been limited. Here, using CRISPR knockout in an in vitro cellular model of syncytiotrophoblast development (BeWo cells), we found that the transcription factor TFEB, mainly known as a regulator of autophagy and lysosomal biogenesis, is required for cell-cell fusion of syncytiotrophoblasts. TFEB translocates to the nucleus, exhibits increased chromatin interactions, and directly binds the Syncytin-1 and Syncytin-2 promoters to control their expression during differentiation. Although TFEB appears to play a critical role in syncytiotrophoblast differentiation, ablation of TFEB largely does not affect lysosomal gene expression or lysosomal biogenesis in differentiating BeWo cells, suggesting a previously uncharacterized role for TFEB in controlling the expression of human syncytins.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"718-737"},"PeriodicalIF":7.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

An old dog with new tricks: TFEB promotes syncytin expression and cell fusion in the human placenta. 老狗玩新花样TFEB 促进人类胎盘中 syncytin 的表达和细胞融合。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-09-19 DOI: 10.1101/gad.352198.124

Stephen J Renaud

引用次数: 0