journal
MENU ▼
Read by QxMD icon Read
search

Genes & Development

journal
https://www.readbyqxmd.com/read/29330354/the-res-complex-is-required-for-efficient-transformation-of-the-precatalytic-b-spliceosome-into-an-activated-bact-complex
#1
Penghui Bao, Cindy L Will, Henning Urlaub, Kum-Loong Boon, Reinhard Lührmann
The precise function of the trimeric retention and splicing (RES) complex in pre-mRNA splicing remains unclear. Here we dissected the role of RES during the assembly and activation of yeast spliceosomes. The efficiency of pre-mRNA splicing was significantly lower in the absence of the RES protein Snu17, and the recruitment of its binding partners, Pml1 (pre-mRNA leakage protein 1) and Bud13 (bud site selection protein 13), to the spliceosome was either abolished or substantially reduced. RES was not required for the assembly of spliceosomal B complexes, but its absence hindered efficient Bact complex formation...
January 12, 2018: Genes & Development
https://www.readbyqxmd.com/read/29330353/afadin-and-rhoa-control-pancreatic-endocrine-mass-via-lumen-morphogenesis
#2
D Berfin Azizoglu, Caitlin Braitsch, Denise K Marciano, Ondine Cleaver
Proper lumen morphogenesis during pancreas development is critical to endocrine and exocrine cell fate. Recent studies showed that a central network of lumens (termed core), but not the surrounding terminal branches (termed periphery), produces most islet endocrine cells. To date, it remains unclear how pancreatic lumens form and remodel and which aspects of lumen morphogenesis influence cell fate. Importantly, models testing the function of the central lumen network as an endocrine niche are lacking. Here, we identify mechanisms underlying lumen formation and remodeling and show that central lumen network morphogenesis impacts pancreatic endocrine mass...
January 12, 2018: Genes & Development
https://www.readbyqxmd.com/read/29330352/dbf4-recruitment-by-forkhead-transcription-factors-defines-an-upstream-rate-limiting-step-in-determining-origin-firing-timing
#3
Dingqiang Fang, Armelle Lengronne, Di Shi, Romain Forey, Magdalena Skrzypczak, Krzysztof Ginalski, Changhui Yan, Xiaoke Wang, Qinhong Cao, Philippe Pasero, Huiqiang Lou
Initiation of eukaryotic chromosome replication follows a spatiotemporal program. The current model suggests that replication origins compete for a limited pool of initiation factors. However, it remains to be answered how these limiting factors are preferentially recruited to early origins. Here, we report that Dbf4 is enriched at early origins through its interaction with forkhead transcription factors Fkh1 and Fkh2. This interaction is mediated by the Dbf4 C terminus and was successfully reconstituted in vitro...
January 12, 2018: Genes & Development
https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#4
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29321179/physiological-protein-blocks-direct-the-mre11-rad50-xrs2-and-sae2-nuclease-complex-to-initiate-dna-end-resection
#5
Giordano Reginato, Elda Cannavo, Petr Cejka
DNA double-strand break repair by homologous recombination is initiated by DNA end resection, which is commenced by the Mre11-Rad50-Xrs2 complex and Sae2 in yeast. Here we report that the nonhomologous end joining factor Ku limits the exonuclease activity of Mre11 and promotes its endonuclease to cleave 5'-terminated DNA strands at break sites. Following initial endonucleolytic cleavage past the obstacle, Exo1 specifically extends the resection track, leading to the generation of long 3' overhangs that are required for homologous recombination...
January 10, 2018: Genes & Development
https://www.readbyqxmd.com/read/29321178/transcription-factor-dependent-anti-repressive-mammalian-enhancers-exclude-h3k27me3-from-extended-genomic-domains
#6
Madhurima Saxena, Adrianna K San Roman, Nicholas K O'Neill, Rita Sulahian, Unmesh Jadhav, Ramesh A Shivdasani
Compacted chromatin and nucleosomes are known barriers to gene expression; the nature and relative importance of other transcriptional constraints remain unclear, especially at distant enhancers. Polycomb repressor complex 2 (PRC2) places the histone mark H3K27me3 predominantly at promoters, where its silencing activity is well documented. In adult tissues, enhancers lack H3K27me3, and it is unknown whether intergenic H3K27me3 deposits affect nearby genes. In primary intestinal villus cells, we identified hundreds of tissue-restricted enhancers that require the transcription factor (TF) CDX2 to prevent the incursion of H3K27me3 from adjoining areas of elevated basal marking into large well-demarcated genome domains...
January 10, 2018: Genes & Development
https://www.readbyqxmd.com/read/29321177/plasticity-of-the-mre11-rad50-xrs2-sae2-nuclease-ensemble-in-the-processing-of-dna-bound-obstacles
#7
Weibin Wang, James M Daley, Youngho Kwon, Danielle S Krasner, Patrick Sung
The budding yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together in DNA end resection during homologous recombination. Here we show that the Ku complex shields DNA ends from exonucleolytic digestion but facilitates endonucleolytic scission by MRX with a dependence on ATP and Sae2. The incision site is enlarged into a DNA gap via the exonuclease activity of MRX, which is stimulated by Sae2 without ATP being present. RPA renders a partially resected or palindromic DNA structure susceptible to MRX-Sae2, and internal protein blocks also trigger DNA cleavage...
January 10, 2018: Genes & Development
https://www.readbyqxmd.com/read/29317486/mutual-dependence-of-the-mrtf-srf-and-yap-tead-pathways-in-cancer-associated-fibroblasts-is-indirect-and-mediated-by-cytoskeletal-dynamics
#8
Charles T Foster, Francesco Gualdrini, Richard Treisman
Both the MRTF-SRF and the YAP-TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF-SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF-SRF and YAP-TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF-SRF genomic targets is also dependent on YAP-TEAD activity, and, conversely, YAP-TEAD target gene expression is also dependent on MRTF-SRF signaling...
January 9, 2018: Genes & Development
https://www.readbyqxmd.com/read/29273679/the-hoxd-cluster-is-a-dynamic-and-resilient-tad-boundary-controlling-the-segregation-of-antagonistic-regulatory-landscapes
#9
Eddie Rodríguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule
The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed...
December 22, 2017: Genes & Development
https://www.readbyqxmd.com/read/29269485/yap-repression-of-the-wnt3-gene-controls-hesc-differentiation-along-the-cardiac-mesoderm-lineage
#10
Conchi Estarás, Hui-Ting Hsu, Ling Huang, Katherine A Jones
Activin/SMAD signaling in human embryonic stem cells (hESCs) ensures NANOG expression and stem cell pluripotency. In the presence of Wnt ligand, the Activin/SMAD transcription network switches to cooperate with Wnt/β-catenin and induce mesendodermal (ME) differentiation genes. We show here that the Hippo effector YAP binds to the WNT3 gene enhancer and prevents the gene from being induced by Activin in proliferating hESCs. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data show that YAP impairs SMAD recruitment and the accumulation of P-TEFb-associated RNA polymerase II (RNAPII) C-terminal domain (CTD)-Ser7 phosphorylation at the WNT3 gene...
December 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/29269483/rna-g-quadruplex-secondary-structure-promotes-alternative-splicing-via-the-rna-binding-protein-hnrnpf
#11
Huilin Huang, Jing Zhang, Samuel E Harvey, Xiaohui Hu, Chonghui Cheng
It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex-forming capacity promote exon inclusion. Destroying G-quadruplex-forming capacity while keeping G tracts intact abrogates exon inclusion. Analysis of RNA-binding protein footprints revealed that G quadruplexes are enriched in heterogeneous nuclear ribonucleoprotein F (hnRNPF)-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome...
December 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/29212662/sharing-the-load-mex67-mtr2-cofunctions-with-los1-in-primary-trna-nuclear-export
#12
Kunal Chatterjee, Shubhra Majumder, Yao Wan, Vijay Shah, Jingyan Wu, Hsiao-Yun Huang, Anita K Hopper
Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export...
December 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/29208645/observation-of-dna-intertwining-along-authentic-budding-yeast-chromosomes
#13
Ainhoa Mariezcurrena, Frank Uhlmann
DNA replication of circular genomes generates physically interlinked or catenated sister DNAs. These are resolved through transient DNA fracture by type II topoisomerases to permit chromosome segregation during cell division. Topoisomerase II is similarly required for linear chromosome segregation, suggesting that linear chromosomes also remain intertwined following DNA replication. Indeed, chromosome resolution defects are a frequent cause of chromosome segregation failure and consequent aneuploidies. When and where intertwines arise and persist along linear chromosomes are not known, owing to the difficulty of demonstrating intertwining of linear DNAs...
December 5, 2017: Genes & Development
https://www.readbyqxmd.com/read/29203645/downstream-promoter-interactions-of-tfiid-tafs-facilitate-transcription-reinitiation
#14
Yoo Jin Joo, Scott B Ficarro, Luis M Soares, Yujin Chun, Jarrod A Marto, Stephen Buratowski
TFIID binds promoter DNA to recruit RNA polymerase II and other basal factors for transcription. Although the TATA-binding protein (TBP) subunit of TFIID is necessary and sufficient for in vitro transcription, the TBP-associated factor (TAF) subunits recognize downstream promoter elements, act as coactivators, and interact with nucleosomes. In yeast nuclear extracts, transcription induces stable TAF binding to downstream promoter DNA, promoting subsequent activator-independent transcription reinitiation. In vivo, promoter responses to TAF mutations correlate with the level of downstream, rather than overall, Taf1 cross-linking...
December 4, 2017: Genes & Development
https://www.readbyqxmd.com/read/29196537/esco1-2-s-roles-in-chromosome-structure-and-interphase-chromatin-organization
#15
Ryotaro Kawasumi, Takuya Abe, Hiroshi Arakawa, Massimiliano Garre, Kouji Hirota, Dana Branzei
ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) are differentially required for genome integrity and development. Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC, while ESCO2 was additionally and specifically required for proliferation and centromere integrity. ESCO1 overexpression fully suppressed the slow proliferation and centromeric separation phenotypes of esco2 cells but only partly suppressed its chromosome arm SCC defects...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29196536/novel-transcriptional-networks-regulated-by-clock-in-human-neurons
#16
Miles R Fontenot, Stefano Berto, Yuxiang Liu, Gordon Werthmann, Connor Douglas, Noriyoshi Usui, Kelly Gleason, Carol A Tamminga, Joseph S Takahashi, Genevieve Konopka
The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29196535/wnk1-kinase-and-the-termination-factor-pcf11-connect-nuclear-mrna-export-with-transcription
#17
Adam Volanakis, Kinga Kamieniarz-Gdula, Margarita Schlackow, Nick J Proudfoot
Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1 phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C-terminal domain (CTD)-interacting domain (CID)...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138280/foxp1-regulation-of-neonatal-vocalizations-via-cortical-development
#18
Noriyoshi Usui, Daniel J Araujo, Ashwinikumar Kulkarni, Marissa Co, Jacob Ellegood, Matthew Harper, Kazuya Toriumi, Jason P Lerch, Genevieve Konopka
The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 are not fully understood. To elucidate the contribution of FOXP1-mediated signaling to brain development and, in particular, neocortical development, we generated forebrain-specific Foxp1 conditional knockout mice...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138279/the-secreted-neurotrophin-sp%C3%A3-tzle-3-promotes-glial-morphogenesis-and-supports-neuronal-survival-and-function
#19
Jaeda C Coutinho-Budd, Amy E Sheehan, Marc R Freeman
Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron-glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia-soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138278/a-cytoplasmic-compass-is-necessary-for-cell-survival-and-triple-negative-breast-cancer-pathogenesis-by-regulating-metabolism
#20
Lu Wang, Clayton K Collings, Zibo Zhao, Kira Alia Cozzolino, Quanhong Ma, Kaiwei Liang, Stacy A Marshall, Christie C Sze, Rintaro Hashizume, Jeffrey Nicholas Savas, Ali Shilatifard
Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7 Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS...
November 14, 2017: Genes & Development
journal
journal
29687
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"