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https://www.readbyqxmd.com/read/28522526/blocking-promiscuous-activation-at-cryptic-promoters-directs-cell-type-specific-gene-expression
#1
Jongmin Kim, Chenggang Lu, Shrividhya Srinivasan, Stephan Awe, Alexander Brehm, Margaret T Fuller
To selectively express cell type-specific transcripts during development, it is critical to maintain genes required for other lineages in a silent state. Here, we show in the Drosophila male germline stem cell lineage that a spermatocyte-specific zinc finger protein, Kumgang (Kmg), working with the chromatin remodeler dMi-2 prevents transcription of genes normally expressed only in somatic lineages. By blocking transcription from normally cryptic promoters, Kmg restricts activation by Aly, a component of the testis-meiotic arrest complex, to transcripts for male germ cell differentiation...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#2
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506985/histone-acetyltransferase-kat8-is-essential-for-mouse-oocyte-development-by-regulating-ros-levels
#3
Shi Yin, Xiaohua Jiang, Hanwei Jiang, Qian Gao, Fang Wang, Suixing Fan, Teka Khan, Nazish Jabeen, Manan Khan, Asim Ali, Peng Xu, Tej K Pandita, Heng-Yu Fan, Yuanwei Zhang, Qinghua Shi
Proper oocyte development is critical for female fertility and requires timely and accurate control of gene expression. K (Lysine) Acetyltransferase 8 (KAT8), an important component of the X chromosome dosage compensation system in Drosophila, regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of Kat8 during mouse oocyte development, we crossed Kat8(flox/flox) mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes. Oocyte Kat8 deletion resulted in female infertility with follicle development failure in the secondary and preantral follicle stages...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28497792/structural-heterogeneity-in-the-intrinsically-disordered-rna-polymerase-ii-c-terminal-domain
#4
Bede Portz, Feiyue Lu, Eric B Gibbs, Joshua E Mayfield, M Rachel Mehaffey, Yan Jessie Zhang, Jennifer S Brodbelt, Scott A Showalter, David S Gilmour
RNA polymerase II contains a repetitive, intrinsically disordered, C-terminal domain (CTD) composed of heptads of the consensus sequence YSPTSPS. The CTD is heavily phosphorylated and serves as a scaffold, interacting with factors involved in transcription initiation, elongation and termination, RNA processing and chromatin modification. Despite being a nexus of eukaryotic gene regulation, the structure of the CTD and the structural implications of phosphorylation are poorly understood. Here we present a biophysical and biochemical interrogation of the structure of the full length CTD of Drosophila melanogaster, which we conclude is a compact random coil...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28477406/metaphase-chromosome-structure-is-dynamically-maintained-by-condensin-i-directed-dna-de-catenation
#5
Ewa Piskadlo, Alexandra Tavares, Raquel A Oliveira
Mitotic chromosome assembly remains a big mystery in biology. Condensin complexes are pivotal for chromosome architecture yet how they shape mitotic chromatin remains unknown. Using acute inactivation approaches and live-cell imaging in Drosophila embryos, we dissect the role of condensin I in the maintenance of mitotic chromosome structure with unprecedented temporal resolution. Removal of condensin I from pre-established chromosomes results in rapid disassembly of centromeric regions while most chromatin mass undergoes hyper-compaction...
May 6, 2017: ELife
https://www.readbyqxmd.com/read/28472469/piwi-interacts-with-chromatin-at-nuclear-pores-and-promiscuously-binds-nuclear-transcripts-in-drosophila-ovarian-somatic-cells
#6
Artem A Ilyin, Sergei S Ryazansky, Semen A Doronin, Oxana M Olenkina, Elena A Mikhaleva, Evgeny Y Yakushev, Yuri A Abramov, Stepan N Belyakin, Anton V Ivankin, Alexey V Pindyurin, Vladimir A Gvozdev, Mikhail S Klenov, Yuri Y Shevelyov
Piwi in a complex with Piwi-interacting RNAs (piRNAs) triggers transcriptional silencing of transposable elements (TEs) in Drosophila ovaries, thus ensuring genome stability. To do this, Piwi must scan the nascent transcripts of genes and TEs for complementarity to piRNAs. The mechanism of this scanning is currently unknown. Here we report the DamID-seq mapping of multiple Piwi-interacting chromosomal domains in somatic cells of Drosophila ovaries. These domains significantly overlap with genomic regions tethered to Nuclear Pore Complexes (NPCs)...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28457869/satellite-repeats-identify-x-chromatin-for-dosage-compensation-in-drosophila-melanogaster-males
#7
Sonal S Joshi, Victoria H Meller
A common feature of sex chromosomes is coordinated regulation of X-linked genes in one sex. Drosophila melanogaster males have one X chromosome, whereas females have two. The resulting imbalance in gene dosage is corrected by increased expression from the single X chromosome of males, a process known as dosage compensation. In flies, compensation involves recruitment of the male-specific lethal (MSL) complex to X-linked genes and modification of chromatin to increase expression. The extraordinary selectivity of the MSL complex for the X chromosome has never been explained...
April 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28436983/stable-polycomb-dependent-transgenerational-inheritance-of-chromatin-states-in-drosophila
#8
Filippo Ciabrelli, Federico Comoglio, Simon Fellous, Boyan Bonev, Maria Ninova, Quentin Szabo, Anne Xuéreb, Christophe Klopp, Alexei Aravin, Renato Paro, Frédéric Bantignies, Giacomo Cavalli
Transgenerational epigenetic inheritance (TEI) describes the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known about the principles and the molecular mechanisms governing this type of inheritance. Here, by transiently enhancing 3D chromatin interactions, we established stable and isogenic Drosophila epilines that carry alternative epialleles, as defined by differential levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming H3K27me3)...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28428611/transcription-factor-antagonism-controls-enteroendocrine-cell-specification-from-intestinal-stem-cells
#9
Yumei Li, Zhimin Pang, Huanwei Huang, Chenhui Wang, Tao Cai, Rongwen Xi
The balanced maintenance and differentiation of local stem cells is required for Homeostatic renewal of tissues. In the Drosophila midgut, the transcription factor Escargot (Esg) maintains undifferentiated states in intestinal stem cells, whereas the transcription factors Scute (Sc) and Prospero (Pros) promote enteroendocrine cell specification. However, the mechanism through which Esg and Sc/Pros coordinately regulate stem cell differentiation is unknown. Here, by combining chromatin immunoprecipitation analysis with genetic studies, we show that both Esg and Sc bind to a common promoter region of pros...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426351/the-absence-of-crossovers-on-chromosome-4-in-drosophila-melanogaster-imperfection-or-interesting-exception
#10
Michaelyn A Hartmann, Jeff Sekelsky
Drosophila melanogaster chromosome 4 is an anomaly because of its small size, chromatin structure, and most notably its lack of crossing over during meiosis. Earlier ideas about the absence of crossovers on 4 hypothesize that these unique characteristics function to prevent crossovers. Here, we explore hypotheses about the absence of crossovers on 4, how these have been addressed, and new insights into the mechanism behind this suppression. We review recently published results that indicate that global crossover patterning, in particular the centromere effect, make a major contribution to the prevention of crossovers on 4...
April 20, 2017: Fly
https://www.readbyqxmd.com/read/28421443/genomic-mapping-of-chromatin-proteins-by-using-dam-inv-modification-of-an-flp-dependent-damid-approach
#11
A V Pindyurin
To identify interactions of chromatin proteins with the genome of the cell type of interest that is a part of heterologous tissues and organs of Drosophila, an FLP-dependent DamID approach was recently developed [4], which does not require sorting of cells or nuclei. Here, a modification of this approach, Dam(inv), is described. The modified approach was validated by generating the binding pattern of the LAM protein, a component of the inner membrane of the nuclear envelope, with the genome of glial cells of the Drosophila larval central brains...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420691/clustering-of-drosophila-housekeeping-promoters-facilitates-their-expression
#12
Marc Corrales-Berjano, Aranzazu Rosado Diez, Ruggero Cortini, Joris van Arensbergen, Bas van Steensel, Guillaume J Filion
Housekeeping genes of animal genomes cluster in the same chromosomal regions. It has long been suggested that this organization contributes to their steady expression across all the tissues of the organism. Here we show that the activity of Drosophila housekeeping gene promoters depends on the expression of their neighbours. By measuring the expression of ~ 85,000 reporters integrated in Kc167 cells, we identified the best predictors of expression as chromosomal contacts with the promoters and terminators of active genes...
April 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#13
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28404631/regulatory-functions-and-chromatin-loading-dynamics-of-linker-histone-h1-during-endoreplication-in-drosophila
#14
Evgeniya N Andreyeva, Travis J Bernardo, Tatyana D Kolesnikova, Xingwu Lu, Lyubov A Yarinich, Boris A Bartholdy, Xiaohan Guo, Olga V Posukh, Sean Healton, Michael A Willcockson, Alexey V Pindyurin, Igor F Zhimulev, Arthur I Skoultchi, Dmitry V Fyodorov
Eukaryotic DNA replicates asynchronously, with discrete genomic loci replicating during different stages of S phase. Drosophila larval tissues undergo endoreplication without cell division, and the latest replicating regions occasionally fail to complete endoreplication, resulting in underreplicated domains of polytene chromosomes. Here we show that linker histone H1 is required for the underreplication (UR) phenomenon in Drosophila salivary glands. H1 directly interacts with the Suppressor of UR (SUUR) protein and is required for SUUR binding to chromatin in vivo...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28398229/controlling-the-master-chromatin-dynamics-at-the-myc-promoter-integrate-developmental-signaling
#15
REVIEW
Olga Zaytseva, Leonie M Quinn
The transcription factor and cell growth regulator MYC is potently oncogenic and estimated to contribute to most cancers. Decades of attempts to therapeutically target MYC directly have not resulted in feasible clinical applications, and efforts have moved toward indirectly targeting MYC expression, function and/or activity to treat MYC-driven cancer. A multitude of developmental and growth signaling pathways converge on the MYC promoter to modulate transcription through their downstream effectors. Critically, even small increases in MYC abundance (<2 fold) are sufficient to drive overproliferation; however, the details of how oncogenic/growth signaling networks regulate MYC at the level of transcription remain nebulous even during normal development...
April 11, 2017: Genes
https://www.readbyqxmd.com/read/28388407/chromatin-architecture-emerges-during-zygotic-genome-activation-independent-of-transcription
#16
Clemens B Hug, Alexis G Grimaldi, Kai Kruse, Juan M Vaquerizas
Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28378812/ecr-recruits-dmi-2-and-increases-efficiency-of-dmi-2-mediated-remodelling-to-constrain-transcription-of-hormone-regulated-genes
#17
Judith Kreher, Kristina Kovač, Karim Bouazoune, Igor Mačinković, Anna Luise Ernst, Erik Engelen, Roman Pahl, Florian Finkernagel, Magdalena Murawska, Ikram Ullah, Alexander Brehm
Gene regulation by steroid hormones plays important roles in health and disease. In Drosophila, the hormone ecdysone governs transitions between key developmental stages. Ecdysone-regulated genes are bound by a heterodimer of ecdysone receptor (EcR) and Ultraspiracle. According to the bimodal switch model, steroid hormone receptors recruit corepressors in the absence of hormone and coactivators in its presence. Here we show that the nucleosome remodeller dMi-2 is recruited to ecdysone-regulated genes to limit transcription...
April 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28367077/protein-and-genetic-composition-of-four-chromatin-types-in-drosophila-melanogaster-cell-lines
#18
Lidiya V Boldyreva, Fyodor P Goncharov, Olga V Demakova, Tatyana Yu Zykova, Victor G Levitsky, Nikolay N Kolesnikov, Alexey V Pindyurin, Valeriy F Semeshin, Igor F Zhimulev
BACKGROUND: Recently, we analyzed genome-wide protein binding data for the Drosophila cell lines S2, Kc, BG3 and Cl.8 (modENCODE Consortium) and identified a set of 12 proteins enriched in the regions corresponding to interbands of salivary gland polytene chromosomes. Using these data, we developed a bioinformatic pipeline that partitioned the Drosophila genome into four chromatin types that we hereby refer to as aquamarine, lazurite, malachite and ruby. RESULTS: Here, we describe the properties of these chromatin types across different cell lines...
April 2017: Current Genomics
https://www.readbyqxmd.com/read/28363744/dref-plays-multiple-roles-during-drosophila-development
#19
REVIEW
Nguyen Trong Tue, Yasuhide Yoshioka, Megumi Mizoguchi, Hideki Yoshida, Mario Zurita, Masamitsu Yamaguchi
DREF was originally identified as a transcription factor that coordinately regulates the expression of DNA replication- and proliferation-related genes in Drosophila. Subsequent studies demonstrated that DREF is involved in tumor suppressor pathways including p53 and Hippo signaling. DREF also regulates the expression of genes encoding components of the JNK and EGFR pathways during Drosophila development. DREF itself is under the control of the TOR pathway during cell and tissue growth responding to nutrition...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28349404/analysis-of-chromatin-dynamics-during-drosophila-spermatogenesis
#20
Tim Hundertmark, Ina Theofel, Zeynep Eren-Ghiani, David Miller, Christina Rathke
In the course of spermatogenesis, germ cells undergo dramatic morphological changes that affect almost all cellular components. Therefore, it is impossible to study the process of spermatogenesis in its entirety without detailed morphological analyses. Here, we describe a method to visualize chromatin dynamics in differentiating Drosophila male germ cells using immunofluorescence staining. In addition, we demonstrate how to treat Drosophila sperm before immunofluorescence staining to help reveal epitopes in the highly condensed sperm chromatin that otherwise may be inaccessible to antibodies...
2017: Methods in Molecular Biology
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