journal
MENU ▼
Read by QxMD icon Read
search

Genes & Development

journal
https://www.readbyqxmd.com/read/29141911/transcriptional-integration-of-mitogenic-and-mechanical-signals-by-myc-and-yap
#1
Ottavio Croci, Serena De Fazio, Francesca Biagioni, Elisa Donato, Marieta Caganova, Laura Curti, Mirko Doni, Silvia Sberna, Deborah Aldeghi, Chiara Biancotto, Alessandro Verrecchia, Daniela Olivero, Bruno Amati, Stefano Campaner
Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP-TEAD act downstream from mitogenic signals, with the latter responding also to mechanical cues. Here, we show that these factors coordinately regulate genes required for cell proliferation. Activation of Myc led to extensive association with its genomic targets, most of which were prebound by TEAD. At these loci, recruitment of YAP was Myc-dependent and led to full transcriptional activation...
November 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138280/foxp1-regulation-of-neonatal-vocalizations-via-cortical-development
#2
Noriyoshi Usui, Daniel J Araujo, Ashwinikumar Kulkarni, Marissa Co, Jacob Ellegood, Matthew Harper, Kazuya Toriumi, Jason P Lerch, Genevieve Konopka
The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 are not fully understood. To elucidate the contribution of FOXP1-mediated signaling to brain development and, in particular, neocortical development, we generated forebrain-specific Foxp1 conditional knockout mice...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138279/the-secreted-neurotrophin-sp%C3%A3-tzle-3-promotes-glial-morphogenesis-and-supports-neuronal-survival-and-function
#3
Jaeda C Coutinho-Budd, Amy E Sheehan, Marc R Freeman
Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron-glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia-soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138278/a-cytoplasmic-compass-is-necessary-for-cell-survival-and-triple-negative-breast-cancer-pathogenesis-by-regulating-metabolism
#4
Lu Wang, Clayton K Collings, Zibo Zhao, Kira Alia Cozzolino, Quanhong Ma, Kaiwei Liang, Stacy A Marshall, Christie C Sze, Rintaro Hashizume, Jeffrey Nicholas Savas, Ali Shilatifard
Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7 Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#5
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138276/metabolic-reprogramming-ensures-cancer-cell-survival-despite-oncogenic-signaling-blockade
#6
Hui-Wen Lue, Jennifer Podolak, Kevin Kolahi, Larry Cheng, Soumya Rao, Devin Garg, Chang-Hui Xue, Juha K Rantala, Jeffrey W Tyner, Kent L Thornburg, Ann Martinez-Acevedo, Jen-Jane Liu, Christopher L Amling, Charles Truillet, Sharon M Louie, Kimberly E Anderson, Michael J Evans, Valerie B O'Donnell, Daniel K Nomura, Justin M Drake, Anna Ritz, George V Thomas
There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29118048/rank-rewires-energy-homeostasis-in-lung-cancer-cells-and-drives-primary-lung-cancer
#7
Shuan Rao, Verena Sigl, Reiner Alois Wimmer, Maria Novatchkova, Alexander Jais, Gabriel Wagner, Stephan Handschuh, Iris Uribesalgo, Astrid Hagelkruys, Ivona Kozieradzki, Luigi Tortola, Roberto Nitsch, Shane J Cronin, Michael Orthofer, Daniel Branstetter, Jude Canon, John Rossi, Manolo D'Arcangelo, Johan Botling, Patrick Micke, Linnea La Fleur, Karolina Edlund, Michael Bergqvist, Simon Ekman, Thomas Lendl, Helmut Popper, Hiroshi Takayanagi, Lukas Kenner, Fred R Hirsch, William Dougall, Josef M Penninger
Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts...
November 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/29074736/molecular-basis-of-cenp-c-association-with-the-cenp-a-nucleosome-at-yeast-centromeres
#8
Hua Xiao, Feng Wang, Jan Wisniewski, Alexey K Shaytan, Rodolfo Ghirlando, Peter C FitzGerald, Yingzi Huang, Debbie Wei, Shipeng Li, David Landsman, Anna R Panchenko, Carl Wu
Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA...
October 26, 2017: Genes & Development
https://www.readbyqxmd.com/read/29021243/zucchini-dependent-pirna-processing-is-triggered-by-recruitment-to-the-cytoplasmic-processing-machinery
#9
Alicia K Rogers, Kathy Situ, Edward M Perkins, Katalin Fejes Toth
The piRNA pathway represses transposable elements in the gonads and thereby plays a vital role in protecting the integrity of germline genomes of animals. Mature piRNAs are processed from longer transcripts, piRNA precursors (pre-piRNAs). In Drosophila, processing of pre-piRNAs is initiated by piRNA-guided Slicer cleavage or the endonuclease Zucchini (Zuc). As Zuc does not have any sequence or structure preferences in vitro, it is not known how piRNA precursors are selected and channeled into the Zuc-dependent processing pathway...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29021240/integrative-genome-analysis-of-somatic-p53-mutant-osteosarcomas-identifies-ets2-dependent-regulation-of-small-nucleolar-rnas-by-mutant-p53-protein
#10
Rasoul Pourebrahim, Yun Zhang, Bin Liu, Ruli Gao, Shunbin Xiong, Patrick P Lin, Mark J McArthur, Michael C Ostrowski, Guillermina Lozano
TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable somatic osteosarcoma mouse model that is initiated with either a single p53 mutation (p53R172H) or p53 loss in osteoblasts. Our study confirmed that p53 mutant mice developed osteosarcomas with increased metastasis as compared with p53-null mice...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29021239/an-rna-binding-protein-qki5-regulates-embryonic-neural-stem-cells-through-pre-mrna-processing-in-cell-adhesion-signaling
#11
Yoshika Hayakawa-Yano, Satoshi Suyama, Masahiro Nogami, Masato Yugami, Ikuko Koya, Takako Furukawa, Li Zhou, Manabu Abe, Kenji Sakimura, Hirohide Takebayashi, Atsushi Nakanishi, Hideyuki Okano, Masato Yano
Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29089423/erratum-rna-binding-proteins-in-neurodegeneration-mechanisms-in-aggregate
#12
Erin G Conlon, James L Manley
No abstract text is available yet for this article.
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29089422/a-cryptic-tudor-domain-links-brwd2-phip-to-compass-mediated-histone-h3k4-methylation
#13
Marc A J Morgan, Ryan A Rickels, Clayton K Collings, Xiaolin He, Kaixiang Cao, Hans-Martin Herz, Kira A Cozzolino, Nebiyu A Abshiru, Stacy A Marshall, Emily J Rendleman, Christie C Sze, Andrea Piunti, Neil L Kelleher, Jeffrey N Savas, Ali Shilatifard
Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29089421/genetic-interrogation-of-replicative-senescence-uncovers-a-dual-role-for-usp28-in-coordinating-the-p53-and-gata4-branches-of-the-senescence-program
#14
Anna E Mazzucco, Agata Smogorzewska, Chanhee Kang, Ji Luo, Michael R Schlabach, Qikai Xu, Rupesh Patel, Stephen J Elledge
Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29089420/genomic-imprinting-of-xist-by-maternal-h3k27me3
#15
Azusa Inoue, Lan Jiang, Falong Lu, Yi Zhang
Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist locus is coated with a broad H3K27me3 domain that is established during oocyte growth and persists through preimplantation development in mice. Loss of maternal H3K27me3 induces maternal Xist expression and maternal XCI in preimplantation embryos. Our study thus identifies maternal H3K27me3 as the imprinting mark of Xist...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29070704/bivalent-complexes-of-prc1-with-orthologs-of-brd4-and-moz-morf-target-developmental-genes-in-drosophila
#16
Hyuckjoon Kang, Youngsook L Jung, Kyle A McElroy, Barry M Zee, Heather A Wallace, Jessica L Woolnough, Peter J Park, Mitzi I Kuroda
Regulatory decisions in Drosophila require Polycomb group (PcG) proteins to maintain the silent state and Trithorax group (TrxG) proteins to oppose silencing. Since PcG and TrxG are ubiquitous and lack apparent sequence specificity, a long-standing model is that targeting occurs via protein interactions; for instance, between repressors and PcG proteins. Instead, we found that Pc-repressive complex 1 (PRC1) purifies with coactivators Fs(1)h [female sterile (1) homeotic] and Enok/Br140 during embryogenesis. Fs(1)h is a TrxG member and the ortholog of BRD4, a bromodomain protein that binds to acetylated histones and is a key transcriptional coactivator in mammals...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29066500/suppression-of-protein-tyrosine-phosphatase-n23-predisposes-to-breast-tumorigenesis-via-activation-of-fyn-kinase
#17
Siwei Zhang, Gaofeng Fan, Yuan Hao, Molly Hammell, John Erby Wilkinson, Nicholas K Tonks
Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various human cancers, including breast cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. In a loss-of-function PTPome screen, our laboratory identified PTPN23 as a suppressor of cell motility and invasion in mammary epithelial and breast cancer cells. Now, our TCGA (The Cancer Genome Atlas) database analyses illustrate a correlation between low PTPN23 expression and poor survival in breast cancers of various subtypes...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29066499/a-mutually-exclusive-stem-loop-arrangement-in-rox2-rna-is-essential-for-x-chromosome-regulation-in-drosophila
#18
Ibrahim Avsar Ilik, Daniel Maticzka, Plamen Georgiev, Noel Marie Gutierrez, Rolf Backofen, Asifa Akhtar
The X chromosome provides an ideal model system to study the contribution of RNA-protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity purification) methodology, which provides unprecedented information about RNA secondary structures in vivo, we identified the minimal functional unit of roX2 RNA...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29051390/corrigendum-the-histone-h2b-specific-ubiquitin-ligase-rnf20-hbre1-acts-as-a-putative-tumor-suppressor-through-selective-regulation-of-gene-expression
#19
Efrat Shema, Itay Tirosh, Yael Aylon, Jing Huang, Chaoyang Ye, Neta Moskovits, Nina Raver-Shapira, Neri Minsky, Judith Pirngruber, Gabi Tarcic, Pavla Hublarova, Lilach Moyal, Mali Gana-Weisz, Yosef Shiloh, Yossef Yarden, Steven A Johnsen, Borivoj Vojtesek, Shelley L Berger, Moshe Oren
No abstract text is available yet for this article.
September 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/29051389/new-genes-often-acquire-male-specific-functions-but-rarely-become-essential-in-drosophila
#20
Shu Kondo, Jeffrey Vedanayagam, Jaaved Mohammed, Sogol Eizadshenass, Lijuan Kan, Nan Pang, Rajaguru Aradhya, Adam Siepel, Josefa Steinhauer, Eric C Lai
Relatively little is known about the in vivo functions of newly emerging genes, especially in metazoans. Although prior RNAi studies reported prevalent lethality among young gene knockdowns, our phylogenomic analyses reveal that young Drosophila genes are frequently restricted to the nonessential male reproductive system. We performed large-scale CRISPR/Cas9 mutagenesis of "conserved, essential" and "young, RNAi-lethal" genes and broadly confirmed the lethality of the former but the viability of the latter...
September 15, 2017: Genes & Development
journal
journal
29687
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"