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Genes & Development

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https://www.readbyqxmd.com/read/28487408/recruitment-of-a-sumo-isopeptidase-to-rdna-stabilizes-silencing-complexes-by-opposing-sumo-targeted-ubiquitin-ligase-activity
#1
Jason Liang, Namit Singh, Christopher R Carlson, Claudio P Albuquerque, Kevin D Corbett, Huilin Zhou
Post-translational modification by SUMO (small ubiquitin-like modifier) plays important but still poorly understood regulatory roles in eukaryotic cells, including as a signal for ubiquitination by SUMO targeted ubiquitin ligases (STUbLs). Here, we delineate the molecular mechanisms for SUMO-dependent control of ribosomal DNA (rDNA) silencing through the opposing actions of a STUbL (Slx5:Slx8) and a SUMO isopeptidase (Ulp2). We identify a conserved region in the Ulp2 C terminus that mediates its specificity for rDNA-associated proteins and show that this region binds directly to the rDNA-associated protein Csm1...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28487407/acute-inactivation-of-the-replicative-helicase-in-human-cells-triggers-mcm8-9-dependent-dna-synthesis
#2
Toyoaki Natsume, Kohei Nishimura, Sheroy Minocherhomji, Rahul Bhowmick, Ian D Hickson, Masato T Kanemaki
DNA replication fork progression can be disrupted at difficult to replicate loci in the human genome, which has the potential to challenge chromosome integrity. This replication fork disruption can lead to the dissociation of the replisome and the formation of DNA damage. To model the events stemming from replisome dissociation during DNA replication perturbation, we used a degron-based system for inducible proteolysis of a subunit of the replicative helicase. We show that MCM2-depleted cells activate a DNA damage response pathway and generate replication-associated DNA double-strand breaks (DSBs)...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28487406/set1a-compass-and-shadow-enhancers-in-the-regulation-of-homeotic-gene-expression
#3
Kaixiang Cao, Clayton K Collings, Stacy A Marshall, Marc A Morgan, Emily J Rendleman, Lu Wang, Christie C Sze, Tianjiao Sun, Elizabeth T Bartom, Ali Shilatifard
The homeotic (Hox) genes are highly conserved in metazoans, where they are required for various processes in development, and misregulation of their expression is associated with human cancer. In the developing embryo, Hox genes are activated sequentially in time and space according to their genomic position within Hox gene clusters. Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#4
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28465358/mutant-idh1-regulates-the-tumor-associated-immune-system-in-gliomas
#5
Nduka M Amankulor, Youngmi Kim, Sonali Arora, Julia Kargl, Frank Szulzewsky, Mark Hanke, Daciana H Margineantu, Aparna Rao, Hamid Bolouri, Jeff Delrow, David Hockenbery, A McGarry Houghton, Eric C Holland
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28465357/identification-of-hair-shaft-progenitors-that-create-a-niche-for-hair-pigmentation
#6
Chung-Ping Liao, Reid C Booker, Sean J Morrison, Lu Q Le
Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512239/erratum-braf-signaling-principles-unveiled-by-large-scale-human-mutation-analysis-with-a-rapid-lentivirus-based-gene-replacement-method
#7
Chae-Seok Lim, Xi Kang, Vincent Mirabella, Huaye Zhang, Qian Bu, Yoichi Araki, Elizabeth T Hoang, Shiqiang Wang, Ying Shen, Sukwoo Choi, Bong-Kiun Kaang, Qiang Chang, Zhiping P Pang, Richard L Huganir, J Julius Zhu
No abstract text is available yet for this article.
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512238/corrigendum-evolution-of-a-transcriptional-regulator-from-a-transmembrane-nucleoporin
#8
Tobias M Franks, Chris Benner, Iñigo Narvaiza, Maria C N Marchetto, Janet M Young, Harmit S Malik, Fred H Gage, Martin W Hetzer
No abstract text is available yet for this article.
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512237/regulation-of-dna-demethylation-by-the-xpc-dna-repair-complex-in-somatic-and-pluripotent-stem-cells
#9
Jaclyn J Ho, Claudia Cattoglio, David T McSwiggen, Robert Tjian, Yick W Fong
Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent state during cellular reprogramming requires DNA methylation to silence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcription. The removal of methylated cytosines requires the base excision repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation occurs in a rapid and site-specific manner remains unclear. Here we show that the XPC DNA repair complex is a potent accelerator of global and locus-specific DNA demethylation in somatic and pluripotent stem cells...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512236/focus-on-cutaneous-and-uveal-melanoma-specificities
#10
REVIEW
Charlotte Pandiani, Guillaume E Béranger, Justine Leclerc, Robert Ballotti, Corine Bertolotto
Cutaneous melanoma (CM) and uveal melanoma (UM) derive from cutaneous and uveal melanocytes that share the same embryonic origin and display the same cellular function. However, the etiopathogenesis and biological behaviors of these melanomas are very different. CM and UM display distinct landscapes of genetic alterations and show different metastatic routes and tropisms. Hence, therapeutic improvements achieved in the last few years for the treatment of CM have failed to ameliorate the clinical outcomes of patients with UM...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512235/identifying-the-niche-controlling-melanocyte-differentiation
#11
REVIEW
Manuel Zocco, Cédric Blanpain
Melanocytes present in hair follicles are responsible for their pigmentation. Melanocyte differentiation and hair pigmentation depend on the stem cell factor (SCF)/c-Kit signaling pathway, but the niche that regulates melanocyte differentiation is not well characterized. In this issue of Genes & Development, Liao and colleagues (pp. 744-756) identify Krox20(+)-derived cells of the hair shaft as the niche and the essential source of SCF required for melanocyte maturation. This study delineates the niche factors regulating melanocyte differentiation and hair pigmentation and opens up new avenues to further characterize the cross-talk between the hair follicle and melanocytes that controls melanocyte maintenance and differentiation...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28512234/a-guide-for-targeted-sumo-removal
#12
REVIEW
Nalini Dhingra, Xiaolan Zhao
SUMO homeostasis is important for many cellular processes. In the current issue of Genes & Development, Liang and colleagues (pp. 802-815) demonstrate how a desumoylation enzyme is targeted to the nucleolus for removing SUMO from specific substrates and how curtailing sumoylation levels can regulate transcription in this nuclear compartment.
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446598/the-histone-variant-h2a-z-promotes-efficient-cotranscriptional-splicing-in-s-cerevisiae
#13
Lauren T Neves, Stephen Douglass, Roberto Spreafico, Srivats Venkataramanan, Tracy L Kress, Tracy L Johnson
In eukaryotes, a dynamic ribonucleic protein machine known as the spliceosome catalyzes the removal of introns from premessenger RNA (pre-mRNA). Recent studies show the processes of RNA synthesis and RNA processing to be spatio-temporally coordinated, indicating that RNA splicing takes place in the context of chromatin. H2A.Z is a highly conserved histone variant of the canonical histone H2A. In Saccharomyces cerevisiae, H2A.Z is deposited into chromatin by the SWR-C complex, is found near the 5' ends of protein-coding genes, and has been implicated in transcription regulation...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446597/the-histone-variant-h2a-z-promotes-splicing-of-weak-introns
#14
Kelly E Nissen, Christina M Homer, Colm J Ryan, Michael Shales, Nevan J Krogan, Kristin L Patrick, Christine Guthrie
Multiple lines of evidence implicate chromatin in the regulation of premessenger RNA (pre-mRNA) splicing. However, the influence of chromatin factors on cotranscriptional splice site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast Schizosaccharomyces pombe Using epistatic miniarray profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446596/dicer-loss-and-recovery-induce-an-oncogenic-switch-driven-by-transcriptional-activation-of-the-oncofetal-imp1-3-family
#15
Courtney K JnBaptiste, Allan M Gurtan, Kevin K Thai, Victoria Lu, Arjun Bhutkar, Mei-Ju Su, Asaf Rotem, Tyler Jacks, Phillip A Sharp
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression critical for organismal viability. Changes in miRNA activity are common in cancer, but how these changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated by miRNAs. We present analysis of the gene expression and phenotypic changes associated with global miRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genes Imp1, Imp2, and Imp3 (Imp1-3) that is up-regulated primarily transcriptionally >100-fold upon Dicer loss and is resistant to resilencing by complete restoration of miRNA activity...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446595/dna-damage-signaling-mediates-the-functional-antagonism-between-replicative-senescence-and-terminal-muscle-differentiation
#16
Lucia Latella, Alessandra Dall'Agnese, Francesca Boscolo Sesillo, Chiara Nardoni, Marianna Cosentino, Armin Lahm, Alessandra Sacco, Pier Lorenzo Puri
The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that, in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated activation of the myogenic program...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446594/pioneering-ebf2-remodels-the-brown-fat-chromatin-landscape
#17
Jiexin Wang, Peter Tontonoz
In this issue of Genes & Development, Shapira and colleagues (pp. 660-673) outline mechanisms by which the brown fat transcription factor early B-cell factor 2 (EBF2) selectively activates brown lineage-specific gene expression. The investigators show that EBF2 interacts with and recruits a tissue-specific BAF chromatin remodeling complex to brown fat gene enhancers, thereby regulating chromatin accessibility. Their findings provide important insight into epigenetic regulation of adipocyte fate and thermogenic gene expression...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446593/creating-cell-type-specific-mutants-by-enhancer-mutagenesis
#18
Stephen Crews
Cell signaling plays an essential role in development, and knowledge of the identities of the cells sending the signal is critical. This can be a challenge, since signaling pathways and ligands are commonly used at multiple times and in multiple cell types during development. One solution to this problem is to create cell type-specific mutants using CRISPR/Cas9 to mutate enhancers that control different patterns of expression. In this issue of Genes & Development, Rogers and colleagues (pp. 634-638) provide the first use of this method in Drosophila to solve a long-standing issue in patterning of the embryonic central nervous system...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28428263/different-requirements-of-functional-telomeres-in-neural-stem-cells-and-terminally-differentiated-neurons
#19
Anastasia Lobanova, Robert She, Simon Pieraut, Charlie Clapp, Anton Maximov, Eros Lazzerini Denchi
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28428262/uncoupling-neurogenic-gene-networks-in-the-drosophila-embryo
#20
William A Rogers, Yogesh Goyal, Kei Yamaya, Stanislav Y Shvartsman, Michael S Levine
The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective (ind). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity...
April 1, 2017: Genes & Development
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