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Deborah M Hinton
Despite recent advances in structural analysis, it is still challenging to obtain a high resolution structure for a complex of RNA polymerase, transcriptional factors, and DNA. However, using biochemical constraints, 3-D printed models of available structures, and computer modeling, one can build biologically relevant models of such supramolecular complexes.
February 2, 2017: Transcription
Nan Hao, Adam C Palmer, Ian B Dodd, Keith E Shearwin
Transcriptional interference (TI) is increasingly recognised as a widespread mechanism of gene control, particularly given the pervasive nature of transcription, both sense and antisense, across all kingdoms of life. Here we discuss how transcription factor binding kinetics strongly influence the ability of a transcription factor to induce or relieve TI.
January 27, 2017: Transcription
Alisa Fuchs, Marcos Torroba, Sarah Kinkley
We recently identified PHF13 as an H3K4me2/3 chromatin reader and transcriptional co-regulator. We found that PHF13 interacts with RNAPIIS5P and PRC2 stabilizing their association with active and bivalent promoters. Furthermore, mass spectrometry analysis identified ∼50 spliceosomal proteins in PHF13s interactome. Here, we will discuss the potential role of PHF13 in RNAPII pausing and co-transcriptional splicing.
January 19, 2017: Transcription
You Li, Min Liu, Lin-Feng Chen, Ruichuan Chen
The release of a paused Pol II depends on the recruitment of P-TEFb. Recent studies showed that both active P-TEFb and inactive P-TEFb (7SK snRNP) can be recruited to the promoter regions of global genes by different mechanisms. Here, we summarize the recent advances on these distinct recruitment mechanisms.
January 19, 2017: Transcription
Pamela Gamba, Katherine James, Nikolay Zenkin
Pausing by RNA polymerase is a major mechanism that regulates transcription elongation but can cause conflicts with fellow RNA polymerases and other cellular machineries. Here, we summarize our recent finding that misincorporation could be a major source of transcription pausing in vivo, and discuss the role of misincorporation-induced pausing.
January 10, 2017: Transcription
Maximilian F Blank, Ingrid Grummt
SIRT7, a member of the sirtuin family of NAD(+)-dependent protein deacetylases, is a key mediator of many cellular activities. SIRT7 expression is linked to cell proliferation and oncogenic activity, connecting SIRT7-dependent regulation of ribosome biogenesis with checkpoints controlling cell cycle progression, metabolic homeostasis, stress resistance, aging and tumorigenesis. Despite this important functional link, the enzymatic activity, the molecular targets and physiological functions of SIRT7 are poorly defined...
January 9, 2017: Transcription
Robert P Fisher
Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the "torpedo" exonuclease Xrn2, which is a CDK substrate...
December 22, 2016: Transcription
Babita Singh, Eduardo Eyras
The functional capacity of cells is defined by the transcriptome. Many recent studies have identified variations in the transcriptome of tumors due to alternative splicing changes, as well as mutations in splicing factors and regulatory signals in most tumor types. Some of these alterations have been linked to tumor progression, metastasis, therapy resistance, and other oncogenic processes. Here, we describe the different mechanisms that drive splicing changes in tumors and their impact in cancer. Motivated by the current evidence, we propose a model whereby a subset of the splicing patterns contributes to the definition of specific tumor phenotypes, and may hold potential for the development of novel clinical biomarkers and therapeutic approaches...
December 22, 2016: Transcription
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
January 2017: Transcription
Eva Nogales, Jie Fang, Robert K Louder
TFIID is a large protein complex required for the recognition and binding of eukaryotic gene core promoter sequences and for the recruitment of the rest of the general transcription factors involved in initiation of eukaryotic protein gene transcription. Cryo-electron microscopy studies have demonstrated the conformational complexity of human TFIID, where one-third of the mass of the complex can shift its position by well over 100 Å. This conformational plasticity appears to be linked to the capacity of TFIID to bind DNA, and suggests how it would allow both the recognition of different core promoter elements and the tuning of its binding affinity by regulatory factors...
January 2017: Transcription
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.
January 2017: Transcription
Madapura M Pradeepa
Enhancers control development and cellular function by spatiotemporal regulation of gene expression. Co-occurrence of acetylation of histone H3 at lysine 27 (H3K27ac) and mono methylation of 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...
January 2017: 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.
January 2017: 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.
January 2017: 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 recruits to the promoter of downregulated 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...
January 2017: Transcription
Pablo Armas, Aldana David, Nora B 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.
January 2017: 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.
January 2017: 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.
January 2017: 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
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
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