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Genes & Development

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https://www.readbyqxmd.com/read/28223312/natural-variation-and-dosage-of-the-hei10-meiotic-e3-ligase-control-arabidopsis-crossover-recombination
#1
Piotr A Ziolkowski, Charles J Underwood, Christophe Lambing, Marina Martinez-Garcia, Emma J Lawrence, Liliana Ziolkowska, Catherine Griffin, Kyuha Choi, F Chris H Franklin, Robert A Martienssen, Ian R Henderson
During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28223311/single-tumor-initiating-cells-evade-immune-clearance-by-recruiting-type-ii-macrophages
#2
Xiaocan Guo, Yang Zhao, Huan Yan, Yingcheng Yang, Shuying Shen, Xiaoming Dai, Xinyan Ji, Fubo Ji, Xing-Guo Gong, Li Li, Xueli Bai, Xin-Hua Feng, Tingbo Liang, Junfang Ji, Lei Chen, Hongyang Wang, Bin Zhao
Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167503/ubiquitylation-activates-a-peptidase-that-promotes-cleavage-and-destabilization-of-its-activating-e3-ligases-and-diverse-growth-regulatory-proteins-to-limit-cell-proliferation-in-arabidopsis
#3
Hui Dong, Jack Dumenil, Fu-Hao Lu, Li Na, Hannes Vanhaeren, Christin Naumann, Maria Klecker, Rachel Prior, Caroline Smith, Neil McKenzie, Gerhard Saalbach, Liangliang Chen, Tian Xia, Nathalie Gonzalez, Mathilde Seguela, Dirk Inze, Nico Dissmeyer, Yunhai Li, Michael W Bevan
The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway...
February 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167502/a-genetic-interaction-analysis-identifies-cancer-drivers-that-modify-egfr-dependency
#4
Sida Liao, Teresa Davoli, Yumei Leng, Mamie Z Li, Qikai Xu, Stephen J Elledge
A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which they can substitute for each other have not been systematically explored. To comprehensively investigate how cancer drivers genetically interact, we searched for modifiers of epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, and expression screens in a non-small cell lung cancer (NSCLC) model. We elucidated a broad spectrum of tumor suppressor genes (TSGs) and oncogenes (OGs) that can genetically modify proliferation and survival of cancer cells when EGFR signaling is altered...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167501/comprehensive-characterization-of-neutrophil-genome-topology
#5
Yina Zhu, Ke Gong, Matthew Denholtz, Vivek Chandra, Mark P Kamps, Frank Alber, Cornelis Murre
Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topologically associating domains (TADs). However, neutrophil genomes were enriched for long-range genomic interactions that spanned multiple TADs. Population-based simulation of spherical and toroid genomes revealed declining radii of gyration for neutrophil chromosomes...
February 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167500/mirnas-cooperate-in-apoptosis-regulation-during-c-elegans-development
#6
Ryan Sherrard, Sebastian Luehr, Heinke Holzkamp, Katherine McJunkin, Nadin Memar, Barbara Conradt
Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of egl-1 is dependent on binding sites for miR-35 and miR-58 family miRNAs within the egl-1 3' untranslated region (UTR), which affect both mRNA copy number and translation...
February 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28202540/sorting-out-adipocyte-precursors-and-their-role-in-physiology-and-disease
#7
REVIEW
Chelsea Hepler, Lavanya Vishvanath, Rana K Gupta
The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28202539/parps-and-adp-ribosylation-recent-advances-linking-molecular-functions-to-biological-outcomes
#8
REVIEW
Rebecca Gupte, Ziying Liu, W Lee Kraus
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28202538/targeting-rna-for-processing-or-destruction-by-the-eukaryotic-rna-exosome-and-its-cofactors
#9
REVIEW
John C Zinder, Christopher D Lima
The eukaryotic RNA exosome is an essential and conserved protein complex that can degrade or process RNA substrates in the 3'-to-5' direction. Since its discovery nearly two decades ago, studies have focused on determining how the exosome, along with associated cofactors, achieves the demanding task of targeting particular RNAs for degradation and/or processing in both the nucleus and cytoplasm. In this review, we highlight recent advances that have illuminated roles for the RNA exosome and its cofactors in specific biological pathways, alongside studies that attempted to dissect these activities through structural and biochemical characterization of nuclear and cytoplasmic RNA exosome complexes...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28202537/in-search-of-the-mechanism-that-shapes-the-neutrophil-s-nucleus
#10
REVIEW
Katia Georgopoulos
The organization of the genome within the confines of the nuclear compartment is considered a key contributor to transcription and DNA replication, repair, and recombination. A typical higher eukaryotic cell has a spherical nucleus that is ∼10 µm in diameter. This is not the case for a neutrophil, a short-lived innate immune cell with an unusual multilobular nuclear structure that may serve purposes outside nuclear functions. In this issue of Genes & Development, Zhu and colleagues (pp. 141-153) investigate the neutrophil's genome organization and the mechanisms that contribute to its unique nuclear shape...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28174210/a-single-transcription-factor-is-sufficient-to-induce-and-maintain-secretory-cell-architecture
#11
Hei-Yong G Lo, Ramon U Jin, Greg Sibbel, Dengqun Liu, Anju Karki, Matthew S Joens, Blair B Madison, Bo Zhang, Valerie Blanc, James A J Fitzpatrick, Nicholas O Davidson, Stephen F Konieczny, Jason C Mills
We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28143833/the-senescence-associated-secretory-phenotype-induces-cellular-plasticity-and-tissue-regeneration
#12
Birgit Ritschka, Mekayla Storer, Alba Mas, Florian Heinzmann, Mari Carmen Ortells, Jennifer P Morton, Owen J Sansom, Lars Zender, William M Keyes
Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete a variety of proteins collectively known as the senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senescence in a paracrine manner. However, the SASP has also been shown to favor embryonic development, wound healing, and even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions of the SASP in promoting a proregenerative response through the induction of cell plasticity and stemness...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28130345/the-piddosome-activates-p53-in-response-to-supernumerary-centrosomes
#13
Luca L Fava, Fabian Schuler, Valentina Sladky, Manuel D Haschka, Claudia Soratroi, Lisa Eiterer, Egon Demetz, Guenter Weiss, Stephan Geley, Erich A Nigg, Andreas Villunger
Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28130344/putting-phds-to-work-phf11-clears-the-way-for-exo1-in-double-strand-break-repair
#14
REVIEW
Karl E Zahn, Roger A Greenberg
In this issue of Genes & Development, Gong and colleagues (pp. 46-58) bring to light a functional role for plant homeodomain finger 11 (PHF11) in 5' end resection at DNA double-strand breaks (DSBs). Using the proteomics of isolated chromatin segments (PICh) technique to purify deprotected telomeres, PHF11 was enriched as cells mounted a DNA damage response (DDR) against exposed chromosome ends. The study reveals interactions between PHF11 and multiple DNA repair proteins and suggests that PHF11 mediates 5' end resection by negotiating RPA-coated DNA repair intermediates...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28130343/finding-the-start-site-redefining-the-human-initiator-element
#15
REVIEW
Jennifer F Kugel, James A Goodrich
Transcription by RNA polymerase II (Pol II) is dictated in part by core promoter elements, which are DNA sequences flanking the transcription start site (TSS) that help direct the proper initiation of transcription. Taking advantage of recent advances in genome-wide sequencing approaches, Vo ngoc and colleagues (pp. 6-11) identified transcripts with focused sites of initiation and found that many were transcribed from promoters containing a new consensus sequence for the human initiator (Inr) core promoter element...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28115468/live-cell-analysis-of-dna-methylation-during-sexual-reproduction-in-arabidopsis-reveals-context-and-sex-specific-dynamics-controlled-by-noncanonical-rddm
#16
Mathieu Ingouff, Benjamin Selles, Caroline Michaud, Thiet M Vu, Frédéric Berger, Andrea J Schorn, Daphné Autran, Matthias Van Durme, Moritz K Nowack, Robert A Martienssen, Daniel Grimanelli
Cytosine methylation is a key epigenetic mark in many organisms, important for both transcriptional control and genome integrity. While relatively stable during somatic growth, DNA methylation is reprogrammed genome-wide during mammalian reproduction. Reprogramming is essential for zygotic totipotency and to prevent transgenerational inheritance of epimutations. However, the extent of DNA methylation reprogramming in plants remains unclear. Here, we developed sensors reporting with single-cell resolution CG and non-CG methylation in Arabidopsis...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28115467/phf11-promotes-dsb-resection-atr-signaling-and-hr
#17
Yi Gong, Naofumi Handa, Stephen C Kowalczykowski, Titia de Lange
Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3' ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5' end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28115466/loss-of-maternal-trim28-causes-male-predominant-early-embryonic-lethality
#18
Abhishek Sampath Kumar, Michelle K Y Seah, Ka Yi Ling, Yaju Wang, Joel H L Tan, Sandra Nitsch, Shu Ly Lim, Chanchao Lorthongpanich, Heike Wollmann, Diana H P Low, Ernesto Guccione, Daniel M Messerschmidt
Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood. Here we show that the Y-linked gene Rbmy1a1 is highly methylated in mature sperm and resists DNA demethylation post-fertilization...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28115465/targeted-crispr-disruption-reveals-a-role-for-rnase-mrp-rna-in-human-preribosomal-rna-processing
#19
Katherine C Goldfarb, Thomas R Cech
MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR-Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor-analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing-implicates MRP RNA in pre-rRNA processing...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28108474/the-human-initiator-is-a-distinct-and-abundant-element-that-is-precisely-positioned-in-focused-core-promoters
#20
Long Vo Ngoc, California Jack Cassidy, Cassidy Yunjing Huang, Sascha H C Duttke, James T Kadonaga
DNA sequence signals in the core promoter, such as the initiator (Inr), direct transcription initiation by RNA polymerase II. Here we show that the human Inr has the consensus of BBCA+1BW at focused promoters in which transcription initiates at a single site or a narrow cluster of sites. The analysis of 7678 focused transcription start sites revealed 40% with a perfect match to the Inr and 16% with a single mismatch outside of the CA+1 core. TATA-like sequences are underrepresented in Inr promoters. This consensus is a key component of the DNA sequence rules that specify transcription initiation in humans...
January 1, 2017: Genes & Development
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