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The last 50 bibliographies

Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription.

Author(s) : Rivosecchi J, Larochelle M, Teste C, Grenier F, Malapert A, Ricci E, Bernard P, Bachand F, Vanoosthuyse V,
Journal : EMBO J
2019
R-loop disassembly by the human helicase Senataxin contributes to genome integrity and to proper transcription termination at a subset of RNA polymerase II genes. Whether Senataxin also contributes to transcription termination at other classes of genes has remained unclear. Here, we show that Sen1, one of twofission yeast homologues of Senataxin, promotes efficient termination of RNA polymerase III (RNAP3) transcription in vivo. In the absence of Sen1, RNAP3 accumulates downstream of RNAP3-transcribed genes and produces long exosome-sensitive 3'-extended transcripts. Importantly, neither of these defectswas affected by the removal of R-loops. The finding that Sen1 acts as an ancillary factor for RNAP3 transcription termination in vivo challenges the pre-existing view that RNAP3 terminates transcription autonomously. We propose that Sen1 is a cofactor for transcription termination that has been co-opted by different RNA polymerases in the course of evolution.

A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair.

Author(s) : Marnef A, Finoux A, Arnould C, Guillou E, Daburon V, Rocher V, Mangeat T, Mangeot P, Ricci E, Legube G,
Journal : Genes Dev
2019
The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. DNA double-strand breaks (DSBs) within rDNA induce both rDNA transcriptional repression and nucleolar segregation, but the link between the two events remains unclear. Here we found that DSBs induced on rDNA trigger transcriptional repression in a cohesin- and HUSH (human silencing hub) complex-dependent manner throughout the cell cycle. In S/G2 cells, transcriptional repression is further followed by extended resection within the interior of the nucleolus, DSB mobilization at the nucleolar periphery within nucleolar caps, and repair by homologous recombination. We showed that nuclear envelope invaginations frequently connect the nucleolus and that rDNA DSB mobilization, but not transcriptional repression, involves the nuclear envelope-associated LINC complex and the actin pathway. Altogether, our data indicate that rDNA break localization at the nucleolar periphery is not a directconsequence of transcriptional repression but rather is an active process that shares features with the mobilization of persistent DSB in active genes and heterochromatin.

The long noncoding RNA CHROME regulates cholesterol homeostasis in primate.

Author(s) : Hennessy E, van Solingen C, Scacalossi K, Ouimet M, Afonso M, Prins J, Koelwyn G, Sharma M, Ramkhelawon B, Carpenter S, Busch A, Chernogubova E, Matic L, Hedin U, Maegdefessel L, Caffrey B, Hussein M, Ricci E, Temel R, Garabedian M, Berger J, Vickers K, Kanke M, Sethupathy P, Teupser D, Holdt L, Moore K,
Journal : Nat Metab
2019
The human genome encodes thousands of long non-coding RNAs (lncRNAs), the majority of which are poorly conserved and uncharacterized. Here we identify a primate-specific lncRNA (CHROME), elevated in the plasma and atherosclerotic plaques of individuals with coronary artery disease, that regulates cellular andsystemic cholesterol homeostasis. LncRNA CHROME expression is influenced by dietary and cellular cholesterol via the sterol-activated liver X receptor transcription factors, which control genes mediating responses to cholesterol overload. Using gain- and loss-of-function approaches, we show that CHROME promotes cholesterol efflux and HDL biogenesis by curbing the actions of a set of functionally related microRNAs that repress genes in those pathways. CHROME knockdown in human hepatocytes and macrophages increases levels of miR-27b, miR-33a, miR-33b and miR-128, thereby reducing expression of their overlapping target gene networks and associated biologic functions. In particular, cells lacking CHROME show reduced expression of ABCA1, which regulates cholesterol efflux and nascent HDL particle formation. Collectively, our findings identify CHROME as a central component of the non-coding RNA circuitry controlling cholesterol homeostasis in humans.

Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning

Author(s) : Sadier A, Twarogowska M, Steklíková k, Hayden L, Lambert A, Schneider P, Laudet V, Hovorakova M, Calvez V, Pantalacci S,
Journal : PLOS Biology
2019

Developmental and comparative transcriptomic identification of iridophore contribution to white barring in clownfish.

Author(s) : Salis P, Lorin T, Lewis V, Rey C, Marcionetti A, Escande M, Roux N, Besseau L, Salamin N, Semon M, Parichy D, Volff J, Laudet V,
Journal : Pigment Cell Melanoma Res
2019
Actinopterygian fishes harbor at least eight distinct pigment cell types, leading to a fascinating diversity of colors. Among this diversity, the cellular origin of the white color appears to be linked to several pigment cell types such as iridophores or leucophores. We used the clownfish Amphiprion ocellaris, which has a color pattern consisting of white bars over a darker body, to characterize thepigment cells that underlie the white hue. We observe by electron microscopy that cells in white bars are similar to iridophores. In addition, the transcriptomic signature of clownfish white bars exhibits similarities with that of zebrafish iridophores. We further show by pharmacological treatments that these cells are necessary for the white color. Among the top differentially expressed genes in white skin, we identified several genes (fhl2a, fhl2b, saiyan, gpnmb, and apoD1a) and show that three of them are expressed in iridophores. Finally, we show by CRISPR/Cas9 mutagenesis that these genes are critical for iridophore developmentin zebrafish. Our analyses provide clues to the genomic underpinning of color diversity and allow identification of new iridophore genes in fish.

Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming

Author(s) : Francesconi M, Di Stefano B, Berenguer C, de Andrés-Aguayo L, Plana-Carmona M, Mendez-Lago M, Guillaumet-Adkins A, Rodriguez-Esteban G, Gut M, Gut I, Heyn H, Lehner B, Graf T,
Journal : eLife
2019

Rouse model with transient intramolecular contacts on a timescale of seconds recapitulates folding and fluctuation of yeast chromosomes.

Author(s) : Socol M, Wang R, Jost D, Carrivain P, Vaillant C, Le Cam E, Dahirel V, Normand C, Bystricky K, Victor J, Gadal O, Bancaud A,
Journal : Nucleic Acids Res
2019
DNA folding and dynamics along with major nuclear functions are determined by chromosome structural properties, which remain, thus far, elusive in vivo. Here,we combine polymer modeling and single particle tracking experiments to determine the physico-chemical parameters of chromatin in vitro and in living yeast. We find that the motion of reconstituted chromatin fibers can be recapitulated by the Rouse model using mechanical parameters of nucleosome arrays deduced from structural simulations. Conversely, we report that the Rouse model shows some inconsistencies to analyze the motion and structural properties inferred from yeast chromosomes determined with chromosome conformation capture techniques (specifically, Hi-C). We hence introduce the Rouse model with Transient InternalContacts (RouseTIC), in which random association and dissociation occurs along the chromosome contour. The parametrization of this model by fitting motion and Hi-C data allows us to measure the kinetic parameters of the contact formation reaction. Chromosome contacts appear to be transient; associated to a lifetime of seconds and characterized by an attractive energy of -0.3 to -0.5 kBT. We suggest attributing this energy to the occurrence of histone tail-DNA contacts and notice that its amplitude sets chromosomes in 'theta' conditions, in which they are poised for compartmentalization and phase separation.

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans.

Author(s) : Beurton F, Stempor P, Caron M, Appert A, Dong Y, Chen R, Cluet D, Coute Y, Herbette M, Huang N, Polveche H, Spichty M, Bedet C, Ahringer J, Palladino F,
Journal : Nucleic Acids Res
2019
The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute tocontext dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegansCFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters.