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Genes & Development

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https://www.readbyqxmd.com/read/27920088/suv4-20-activity-in-the-preimplantation-mouse-embryo-controls-timely-replication
#1
André Eid, Diego Rodriguez-Terrones, Adam Burton, Maria-Elena Torres-Padilla
Extensive chromatin remodeling after fertilization is thought to take place to allow a new developmental program to start. This includes dynamic changes in histone methylation and, in particular, the remodeling of constitutive heterochromatic marks such as histone H4 Lys20 trimethylation (H4K20me3). While the essential function of H4K20me1 in preimplantation mouse embryos is well established, the role of the additional H4K20 methylation states through the action of the SUV4-20 methyltransferases has not been addressed...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27920087/structural-visualization-of-the-p53-rna-polymerase-ii-assembly
#2
Sameer K Singh, Zhen Qiao, Lihua Song, Vijay Jani, William Rice, Edward Eng, Robert A Coleman, Wei-Li Liu
The master tumor suppressor p53 activates transcription in response to various cellular stresses in part by facilitating recruitment of the transcription machinery to DNA. Recent studies have documented a direct yet poorly characterized interaction between p53 and RNA polymerase II (Pol II). Therefore, we dissected the human p53/Pol II interaction via single-particle cryo-electron microscopy, structural docking, and biochemical analyses. This study reveals that p53 binds Pol II via the Rpb1 and Rpb2 subunits, bridging the DNA-binding cleft of Pol II proximal to the upstream DNA entry site...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27920086/a-role-for-mitotic-bookmarking-of-sox2-in-pluripotency-and-differentiation
#3
Cédric Deluz, Elias T Friman, Daniel Strebinger, Alexander Benke, Mahé Raccaud, Andrea Callegari, Marion Leleu, Suliana Manley, David M Suter
Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913604/conversion-of-t-cells-to-b-cells-by-inactivation-of-polycomb-mediated-epigenetic-suppression-of-the-b-lineage-program
#4
Tomokatsu Ikawa, Kyoko Masuda, Takaho A Endo, Mitsuhiro Endo, Kyoichi Isono, Yoko Koseki, Rinako Nakagawa, Kohei Kometani, Junichiro Takano, Yasutoshi Agata, Yoshimoto Katsura, Tomohiro Kurosaki, Miguel Vidal, Haruhiko Koseki, Hiroshi Kawamoto
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913603/the-tumor-suppressor-flcn-mediates-an-alternate-mtor-pathway-to-regulate-browning-of-adipose-tissue
#5
Shogo Wada, Michael Neinast, Cholsoon Jang, Yasir H Ibrahim, Gina Lee, Apoorva Babu, Jian Li, Atsushi Hoshino, Glenn C Rowe, James Rhee, José A Martina, Rosa Puertollano, John Blenis, Michael Morley, Joseph A Baur, Patrick Seale, Zoltan Arany
Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dubé syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#6
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27856617/pdgfr%C3%AE-regulates-craniofacial-development-through-homodimers-and-functional-heterodimers-with-pdgfr%C3%AE
#7
Katherine A Fantauzzo, Philippe Soriano
Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor α (PDGFRα) has well-documented functions in this process, the role of PDGFRβ in murine craniofacial development is not well established. We demonstrate that PDGFRα and PDGFRβ are coexpressed in the craniofacial mesenchyme of mid-gestation mouse embryos and that ablation of Pdgfrb in the neural crest lineage results in increased nasal septum width, delayed palatal shelf development, and subepidermal blebbing...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27856616/antisense-transcription-licenses-nascent-transcripts-to-mediate-transcriptional-gene-silencing
#8
Yunkun Dang, Jiasen Cheng, Xianyun Sun, Zhipeng Zhou, Yi Liu
In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and disiRNA locus DNA methylation (DLDM) in Neurospora crassa Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM. Convergent transcription causes stalling of RNA polymerase II during transcription, which permits ERI-1 to bind nascent RNAs in the nucleus and recruit a histone methyltransferase complex that catalyzes chromatin modifications...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27856615/epigenetic-regulation-of-intestinal-stem-cells-by-tet1-mediated-dna-hydroxymethylation
#9
Rinho Kim, Karyn L Sheaffer, Inchan Choi, Kyoung-Jae Won, Klaus H Kaestner
Methylated cytosines are associated with gene silencing. The ten-eleven translocation (TET) hydroxylases, which oxidize methylated cytosines to 5-hydroxymethylcytosine (5hmC), are essential for cytosine demethylation. Gene silencing and activation are critical for intestinal stem cell (ISC) maintenance and differentiation, but the potential role of TET hydroxylases in these processes has not yet been examined. Here, we generated genome-wide maps of the 5hmC mark in ISCs and their differentiated progeny. Genes with high levels of hydroxymethylation in ISCs are strongly associated with Wnt signaling and developmental processes...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27852629/coupled-enhancer-and-coding-sequence-evolution-of-a-homeobox-gene-shaped-leaf-diversity
#10
Francesco Vuolo, Remco A Mentink, Mohsen Hajheidari, C Donovan Bailey, Dmitry A Filatov, Miltos Tsiantis
Here we investigate mechanisms underlying the diversification of biological forms using crucifer leaf shape as an example. We show that evolution of an enhancer element in the homeobox gene REDUCED COMPLEXITY (RCO) altered leaf shape by changing gene expression from the distal leaf blade to its base. A single amino acid substitution evolved together with this regulatory change, which reduced RCO protein stability, preventing pleiotropic effects caused by its altered gene expression. We detected hallmarks of positive selection in these evolved regulatory and coding sequence variants and showed that modulating RCO activity can improve plant physiological performance...
November 16, 2016: Genes & Development
https://www.readbyqxmd.com/read/27881602/n-terminal-acetylation-promotes-synaptonemal-complex-assembly-in-c-elegans
#11
Jinmin Gao, Consuelo Barroso, Pan Zhang, Hyun-Min Kim, Shangtong Li, Leticia Labrador, James Lightfoot, Maxim V Gerashchenko, Vyacheslav M Labunskyy, Meng-Qiu Dong, Enrique Martinez-Perez, Monica P Colaiácovo
N-terminal acetylation of the first two amino acids on proteins is a prevalent cotranslational modification. Despite its abundance, the biological processes associated with this modification are not well understood. Here, we mapped the pattern of protein N-terminal acetylation in Caenorhabditis elegans, uncovering a conserved set of rules for this protein modification and identifying substrates for the N-terminal acetyltransferase B (NatB) complex. We observed an enrichment for global protein N-terminal acetylation and also specifically for NatB substrates in the nucleus, supporting the importance of this modification for regulating biological functions within this cellular compartment...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27881601/structural-basis-for-snrna-recognition-by-the-double-wd40-repeat-domain-of-gemin5
#12
Wenxing Jin, Yi Wang, Chao-Pei Liu, Na Yang, Mingliang Jin, Yao Cong, Mingzhu Wang, Rui-Ming Xu
Assembly of the spliceosomal small nuclear ribonucleoparticle (snRNP) core requires the participation of the multisubunit SMN (survival of motor neuron) complex, which contains SMN and several Gemin proteins. The SMN and Gemin2 subunits directly bind Sm proteins, and Gemin5 is required for snRNP biogenesis and has been implicated in snRNA recognition. The RNA sequence required for snRNP assembly includes the Sm site and an adjacent 3' stem-loop, but a precise understanding of Gemin5's RNA-binding specificity is lacking...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27881600/structural-insights-into-gemin5-guided-selection-of-pre-snrnas-for-snrnp-assembly
#13
Chao Xu, Hideaki Ishikawa, Keiichi Izumikawa, Li Li, Hao He, Yuko Nobe, Yoshio Yamauchi, Hanief M Shahjee, Xian-Hui Wu, Yi-Tao Yu, Toshiaki Isobe, Nobuhiro Takahashi, Jinrong Min
In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)4-6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addition, Gemin5 has been reported to specifically bind to the m(7)G cap. In this study, we show that the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs by isothermal titration calorimetry (ITC) and mutagenesis assays...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27881599/undercover-gene-control-by-metabolites-and-metabolic-enzymes
#14
REVIEW
Jan A van der Knaap, C Peter Verrijzer
To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awareness that central components of intermediary metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such, their concentrations constitute a potential regulatory interface between the metabolic and chromatin states...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27881598/the-right-pick-structural-basis-of-snrna-selection-by-gemin5
#15
Markus C Wahl, Utz Fischer
Macromolecular complexes, rather than individual biopolymers, perform many cellular activities. Faithful assembly of these complexes in vivo is therefore a vital challenge of all cells, and its failure can have fatal consequences. To form functional complexes, cells use elaborate measures to select the "right" components and combine them into working entities. How assembly is achieved at the molecular level is unclear in many cases. Three groups (Jin and colleagues, pp. 2391-2403; Xu and colleagues, pp. 2376-2390; and Tang and colleagues in Cell Research) have now provided insights into how an assembly factor specifically recognizes substrate RNA molecules and enables their usage for assembly of Sm-class uridine-rich small nuclear RNA-protein complexes...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27898395/corrigendum-quantitative-proteomic-analysis-of-purified-yeast-kinetochores-identifies-a-pp1-regulatory-subunit
#16
Bungo Akiyoshi, Christian R Nelson, Jeffrey A Ranish, Sue Biggins
No abstract text is available yet for this article.
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27898394/mef2-transcription-factors-are-key-regulators-of-sprouting-angiogenesis
#17
Natalia Sacilotto, Kira M Chouliaras, Leonid L Nikitenko, Yao Wei Lu, Martin Fritzsche, Marsha D Wallace, Svanhild Nornes, Fernando García-Moreno, Sophie Payne, Esther Bridges, Ke Liu, Daniel Biggs, Indrika Ratnayaka, Shane P Herbert, Zoltán Molnár, Adrian L Harris, Benjamin Davies, Gareth L Bond, George Bou-Gharios, John J Schwarz, Sarah De Val
Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of the endothelium. However, the molecular links between proangiogenic signals and downstream gene expression remain unclear. During sprouting angiogenesis, the specification of endothelial cells into the tip cells that lead new blood vessel sprouts is coordinated by vascular endothelial growth factor A (VEGFA) and Delta-like ligand 4 (Dll4)/Notch signaling and requires high levels of Notch ligand DLL4...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27898393/a-noncanonical-auxin-sensing-mechanism-is-required-for-organ-morphogenesis-in-arabidopsis
#18
Sara Simonini, Joyita Deb, Laila Moubayidin, Pauline Stephenson, Manoj Valluru, Alejandra Freire-Rios, Karim Sorefan, Dolf Weijers, Jiří Friml, Lars Østergaard
Tissue patterning in multicellular organisms is the output of precise spatio-temporal regulation of gene expression coupled with changes in hormone dynamics. In plants, the hormone auxin regulates growth and development at every stage of a plant's life cycle. Auxin signaling occurs through binding of the auxin molecule to a TIR1/AFB F-box ubiquitin ligase, allowing interaction with Aux/IAA transcriptional repressor proteins. These are subsequently ubiquitinated and degraded via the 26S proteasome, leading to derepression of auxin response factors (ARFs)...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27898392/colocalization-of-distant-chromosomal-loci-in-space-in-e-coli-a-bacterial-nucleolus
#19
Tamas Gaal, Benjamin P Bratton, Patricia Sanchez-Vazquez, Alexander Sliwicki, Kristine Sliwicki, Andrew Vegel, Rachel Pannu, Richard L Gourse
The spatial organization of DNA within the bacterial nucleoid remains unclear. To investigate chromosome organization in Escherichia coli, we examined the relative positions of the ribosomal RNA (rRNA) operons in space. The seven rRNA operons are nearly identical and separated from each other by as much as 180° on the circular genetic map, a distance of ≥2 million base pairs. By inserting binding sites for fluorescent proteins adjacent to the rRNA operons and then examining their positions pairwise in live cells by epifluorescence microscopy, we found that all but rrnC are in close proximity...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27898391/replication-fork-instability-and-the-consequences-of-fork-collisions-from-rereplication
#20
REVIEW
Jessica L Alexander, Terry L Orr-Weaver
Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA...
October 15, 2016: Genes & Development
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