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José A Martina, Rosa Puertollano
Cellular adaptation response to a myriad of stressors is key for survival. The lysosomal/autophagy pathway is inextricably connected to the stress response regulation. Two transcription factors, TFEB and TFE3, have recently emerged as master regulators of this degradative pathway. Their function modulating different cellular pathways will be discussed.
November 28, 2016: Transcription
Leonhard Wachutka, Julien Gagneur
We give an overview of experimental and computational methods to estimate RNA metabolism rates genome-wide. We then advocate a local definition of RNA metabolism rate at the level of individual phosphodiester bonds. Rates of formation and disappearance of individual bonds are unambiguously defined, in contrast to rates of complete transcripts. We show that over previous approaches, the recently developed transient transcriptome sequencing (TT-seq) protocol allows for estimation of metabolism rates of individual bonds with least positional bias...
November 14, 2016: Transcription
Madapura M Pradeepa
Enhancers control development and cellular function by spatiotemporal regulation of gene expression. Co-occurance of acetylation at histone H3 at lysine 27 (H3K27ac) and mono methylation at histone H3 at lysine 4 (H3K4me1) has been widely used for identification of active enhancers. However, increasing evidence suggests that using this combination of marks alone for enhancer identification gives an incomplete picture of the active enhancer repertoire. We have shown that the H3 globular domain acetylations - H3K64ac and H3K122ac; and an H4 tail acetylation - H4K16ac are enriched at active enhancers together with H3K27ac, and also at a large number of enhancers without detectable H3K27ac...
October 28, 2016: Transcription
Diego M Presman, Gordon L Hager
It is widely accepted that the glucocorticoid receptor (GR), a ligand-regulated transcription factor that triggers anti-inflammatory responses, binds specific response elements as a homodimer. Here, we will discuss the original primary data that established this model and contrast it with a recent report characterizing the GR-DNA complex as a tetramer.
October 20, 2016: Transcription
Shota Suzuki, Yota Murakami, Shinya Takahata
Epigenetic marks determine cell fate via numerous reader proteins. H3K36 methylation is a common epigenetic mark that is thought to be associated with the activities of the RNA polymerase 2 C-terminal domain. We discuss a novel silencing mechanism regulated by Set2-dependent H3K36 methylation that involves exosome-dependent RNA processing.
October 10, 2016: Transcription
A Silvina Nacht, Miguel Beato, Guillermo P Vicent
How genes are repressed by steroid hormones remains a matter of debate and several indirect mechanisms have been proposed. We found that the ligand-activated progesterone receptor (PR) recruits to the promoter of down-regulated genes a repressor complex composed of HP1γ, the lysine demethylase LSD1, histone deacetylases, coREST, the RNA SRA and the ATPase BRG1. BRG1 is needed for chromatin remodeling and facilitates the deposition of linker histone variant H1.2, which compacts chromatin and hinders RNA polymerase loading and transcription...
October 4, 2016: Transcription
Pablo Armas, Aldana David, Nora Calcaterra
G-quadruplexes are non-canonical DNA secondary structures involved in several genomic and molecular processes. Here we summarize the main G-quadruplex features and evidences proving the in vivo role on the transcriptional regulation of genes required for zebrafish embryonic development. We also discuss alternative strategies for specifically interfering G-quadruplex in vivo.
October 3, 2016: Transcription
Yuanyuan Li, Dan Zhao, Zhonglei Chen, Haitao Li
Recent research reveals that the YEATS domains preferentially recognize crotonylated lysines on histones. Here, we discuss the molecular mechanisms that enable this recognition and the biological significances of this interaction. The dynamics of histone crotonylation and its potential roles in the regulation of gene expression will also be discussed.
September 23, 2016: Transcription
Yuhong Zuo, Thomas A Steitz
During transcription, RNA polymerase moves downstream along the DNA template and maintains a transcription bubble. Several recent structural studies of transcription complexes with a complete transcription bubble provide new insights into how RNAP couples the nucleotide addition reaction to its directional movement.
September 22, 2016: Transcription
Yan Han, Yuan He
The structures of RNA Polymerase (Pol) II pre-initiation complexes (PIC) have recently been determined at near-atomic resolution, elucidating unprecedented mechanistic details of promoter opening during transcription initiation. The key structural features of promoter opening are summarized here. Structural knowledge of Pol I and III PIC is also briefly discussed.
October 19, 2016: Transcription
Robert Root-Bernstein, Yunsoo Kim, Adithya Sanjay, Zachary F Burton
Multiple models have been advanced for the evolution of cloverleaf tRNA. Here, the conserved archaeal tRNA core (75-nt) is posited to have evolved from ligation of three proto-tRNA minihelices (31-nt) and two-symmetrical 9-nt deletions within joined acceptor stems (93 - 18 = 75-nt). The primary evidence for this conclusion is that the 5-nt stem 7-nt anticodon loop and the 5-nt stem 7-nt T loop are structurally homologous and related by coding sequence. We posit that the D loop was generated from a third minihelix (31-nt) in which the stem and loop became rearranged after 9-nt acceptor stem deletions and cloverleaf folding...
October 19, 2016: Transcription
Yuko S Niwa, Ryusuke Niwa
Transcription factors generally regulate gene expression of multiple targets. In contrast, our recent finding suggests that the zinc finger protein Ouija board controls steroid hormone biosynthesis through specific regulation of only one gene spookier in Drosophila. It sheds light on a specialized but essential factor that evolved for one target.
October 19, 2016: Transcription
Abhijeet Pataskar, Vijay K Tiwari
Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.
October 19, 2016: Transcription
Didier Auboeuf
Understanding the molecular mechanisms behind the capacity of cancer cells to adapt to the tumor microenvironment and to anticancer therapies is a major challenge. In this context, cancer is believed to be an evolutionary process where random mutations and the selection process shape the mutational pattern and phenotype of cancer cells. This article challenges the notion of randomness of some cancer-associated mutations by describing molecular mechanisms involving stress-mediated biogenesis of mRNA-derived small RNAs able to target and increase the local mutation rate of the genomic loci they originate from...
August 10, 2016: Transcription
Catherine A Kemme, Dan Nguyen, Abhijnan Chattopadhyay, Junji Iwahara
Eukaryotic genomic DNA contains numerous high-affinity sites for transcription factors. Only a small fraction of these sites directly regulates target genes. Other high-affinity sites can serve as naturally present decoys that sequester transcription factors. Such natural decoys in genomic DNA may provide novel regulatory mechanisms for transcription factors.
August 7, 2016: Transcription
Jörn Lämke, Krzysztof Brzezinka, Isabel Bäurle
In nature, stress is typically chronic or recurring and stress exposure can prime modified responses to recurring stress. Such stress priming may occur at the level of transcription. Here, we discuss the connection between plant stress memory, transcription, and chromatin modifications using the example of recurring heat stress.
August 7, 2016: Transcription
Thomas G Fazzio
Hybridization of RNA to its template DNA strand during transcription induces formation of R-loops-RNA:DNA hybrids with unpaired non-template DNA strands. Although unresolved R-loops can be detrimental, some R-loops contribute to regulation of chromatin structure. Consequently, R-loops help regulate gene expression and play important roles in numerous cellular processes.
August 7, 2016: Transcription
Niklas A Hoffmann, Yashar Sadian, Lucas Tafur, Jan Kosinski, Christoph W Müller
Here, we discuss the overall architecture of the RNA polymerase I (Pol I) and III (Pol III) core enzymes and their associated general transcription factors in the context of models of the Pol I and Pol III pre-initiation complexes, thereby highlighting potential functional adaptations of the Pol I and Pol III enzymes to their respective transcription tasks. Several new insights demonstrate the great degree of specialization of each of the eukaryotic RNA polymerases that is only beginning to be revealed as the structural and functional characterization of all eukaryotic RNA polymerases and their pre-initiation complexes progresses...
August 7, 2016: Transcription
Bruce A Knutson, Marissa L Smith, Nancy Walker-Kopp, Xia Xu
Super elongation complex (SEC) belongs to a family of RNA polymerase II (Pol II) elongation factors that has similar properties as TFIIF, a general transcription factor that increases the transcription elongation rate by reducing pausing. Although SEC has TFIIF-like functional properties, it apparently lacks sequence and structural homology. Using HHpred, we find that SEC contains an evolutionarily related TFIIF-like subcomplex. We show that the SEC subunit ELL interacts with the Pol II Rbp2 subunit, as expected for a TFIIF-like factor...
August 7, 2016: Transcription
Bess Ling Chau, King Pan Ng, Kim K C Li, Kevin A W Lee
The multi-functional TET (TAF15/EWS/TLS) or FET (FUS/EWS/TLS) protein family of higher organisms harbor a transcriptional-activation domain (EAD) and an RNA-binding domain (RBD). The transcriptional activation function is, however, only revealed in oncogenic TET-fusion proteins because in native TET proteins it is auto-repressed by RGG-boxes within the TET RBD. Auto-repression is suggested to involve direct cation-pi interactions between multiple Arg residues within RGG boxes and EAD aromatics. Via analysis of TET transcriptional activity in different organisms, we report herein that repression is not autonomous but instead requires additional trans-acting factors...
August 7, 2016: Transcription
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