Genes & development最新文献_第9页

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

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

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

The MYC-MAF-SAGA axis drives oncogenic gene expression in multiple myeloma. MYC-MAF-SAGA 轴驱动多发性骨髓瘤中致癌基因的表达。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-09-19 DOI: 10.1101/gad.352186.124

Hongkuan Wang, Hong Wen, Xiaobing Shi

引用次数: 0

A cellular identity crisis? Plasticity changes during aging and rejuvenation 细胞身份危机？衰老和年轻化过程中的可塑性变化

IF 10.5 1区生物学

Genes & development Pub Date : 2024-09-18 DOI: 10.1101/gad.351728.124

Rebecca Gorelov, Konrad Hochedlinger

引用次数: 0

Developmental regulation of dermal adipose tissue by BCL11b BCL11b 对真皮脂肪组织的发育调控

IF 10.5 1区生物学

Genes & development Pub Date : 2024-09-12 DOI: 10.1101/gad.351907.124

Sarah Traynor, Shashwati Bhattacharya, Kirill Batmanov, Lan Cheng, Angela Weller, Natalie Moore, Carmen Flesher, David Merrick

{"title":"Developmental regulation of dermal adipose tissue by BCL11b","authors":"Sarah Traynor, Shashwati Bhattacharya, Kirill Batmanov, Lan Cheng, Angela Weller, Natalie Moore, Carmen Flesher, David Merrick","doi":"10.1101/gad.351907.124","DOIUrl":"https://doi.org/10.1101/gad.351907.124","url":null,"abstract":"The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis, we characterized cell populations, including Bcl11b+ cells, that regulate the development of dermal white adipose tissue (dWAT). We discovered that BCL11b expression modulates the Wnt signaling microenvironment to enable adipogenic differentiation in the dermal compartment. Subcutaneous and visceral adipose arises from a distinct population of Nefl+ cells during embryonic organogenesis, whereas Pi16+/Dpp4+ fibroadipogenic progenitors support obesity-stimulated hypertrophic expansion in the adult. Together, these results highlight the unique regulatory pathways used by anatomically distinct adipose depots, with important implications for human metabolic disease.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"20 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175022","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

Arrested development: the dysfunctional life history of medulloblastoma 发育停滞：髓母细胞瘤的功能失调生活史

IF 10.5 1区生物学

Genes & development Pub Date : 2024-09-04 DOI: 10.1101/gad.351936.124

Ran Tao, Katie Han, Stephanie C. Wu, Jake D. Friske, Martine F. Roussel, Paul A. Northcott

引用次数: 0

Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders 异卵RPA2变体是端粒生物学疾病的新型遗传病因

IF 10.5 1区生物学

Genes & development Pub Date : 2024-09-04 DOI: 10.1101/gad.352032.124

Rima Kochman, Ibrahima Ba, Maïlyn Yates, Vithura Pirabakaran, Florian Gourmelon, Dmitri Churikov, Marc Lafaille, Laëtitia Kermasson, Coline Hamelin, Isabelle Marois, Frédéric Jourquin, Laura Braud, Marianne Bechara, Elodie Lainey, Hilario Nunes, Philippe Breton, Morgane Penhouet, Pierre David, Vincent Géli, Christophe Lachaud, Alexandre Maréchal, Patrick Revy, Caroline Kannengiesser, Carole Saintomé, Stéphane Coulon

{"title":"Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders","authors":"Rima Kochman, Ibrahima Ba, Maïlyn Yates, Vithura Pirabakaran, Florian Gourmelon, Dmitri Churikov, Marc Lafaille, Laëtitia Kermasson, Coline Hamelin, Isabelle Marois, Frédéric Jourquin, Laura Braud, Marianne Bechara, Elodie Lainey, Hilario Nunes, Philippe Breton, Morgane Penhouet, Pierre David, Vincent Géli, Christophe Lachaud, Alexandre Maréchal, Patrick Revy, Caroline Kannengiesser, Carole Saintomé, Stéphane Coulon","doi":"10.1101/gad.352032.124","DOIUrl":"https://doi.org/10.1101/gad.352032.124","url":null,"abstract":"Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in RPA2. Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination. Using engineered knock-in cell lines, we found an accumulation of RPA at telomeres that did not trigger ATR activation but caused short and dysfunctional telomeres. Finally, both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening. Collectively, our study indicates that variants in RPA2 represent a novel genetic cause of TBDs. Our results further support the fundamental role of the RPA complex in regulating telomere length and stability in humans.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"19 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130746","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