Frequency of TERT promoter mutations in human cancers

Frequency of TERT promoter mutations in human cancers

by João Vinagre

Article

Reactivation of telomerase has been implicated in human tumorigenesis. Here, somatic mutations in the TERT promoter are reported in cancers of the central nervous system, bladder, follicular cell-derived thyroid and melanoma, thus demonstrating that TERT promoter mutations are a frequent event in human cancer.

Nature Communications doi: 10.1038/ncomms3185

Authors: João Vinagre, Ana Almeida, Helena Pópulo, Rui Batista, Joana Lyra, Vasco Pinto, Ricardo Coelho, Ricardo Celestino, Hugo Prazeres, Luis Lima, Miguel Melo, Adriana Gaspar da Rocha, Ana Preto, Patrícia Castro, Ligia Castro, Fernando Pardal, José Manuel Lopes, Lúcio Lara Santos, Rui Manuel Reis, José Cameselle-Teijeiro, Manuel Sobrinho-Simões, Jorge Lima, Valdemar Máximo, Paula Soares

Local features determine cis-regulatory function [Genetics]

by White, M. A., Myers, C. A., Corbo, J. C., Cohen, B. A.

Transcription factors (TFs) recognize short sequence motifs that are present in millions of copies in large eukaryotic genomes. TFsmust distinguish their target binding sites from a vast genomic excess of spurious motif occurrences; however, it is unclear whether functional sites are distinguished from nonfunctional motifs by local primary sequence features...

DNA-binding site changes in forkhead evolution [Evolution]

DNA-binding site changes in forkhead evolution [Evolution]

by Nakagawa, S., Gisselbrecht, S. S., Rogers, J. M., Hartl, D. L., Bulyk, M. L.

The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and related protists. We have used a combination of maximum-likelihood...

A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design

A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design

by Robin Smith

Background: Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. Results: We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. Conclusions: This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

An Epigenetic Trap Stabilizes Singular Olfactory Receptor Expression

An Epigenetic Trap Stabilizes Singular Olfactory Receptor Expression

David B. Lyons, William E. Allen, Tracie Goh, Lulu Tsai, Gilad Barnea, Stavros Lomvardas. The molecular mechanisms regulating olfactory receptor (OR) expression in the mammalian nose are not yet understood. Here, we identify the transient expression of histone demethylase LSD1 and the ....

SET1 and p300 Act Synergistically, through Coupled Histone Modifications, in Transcriptional Activation by p53

SET1 and p300 Act Synergistically, through Coupled Histone Modifications, in Transcriptional Activation by p53

Zhanyun Tang, Wei-Yi Chen, Miho Shimada, Uyen T.T. Nguyen, Jaehoon Kim, Xiao-Jian Sun, Toru Sengoku, Robert K. McGinty, Joseph P. Fernandez, Tom W. Muir, Robert G. Roeder. The H3K4me3 mark in chromatin is closely correlated with actively transcribed genes, although the mechanisms involved in its generation and function are not fully understood. In vitro studies with....

Ectopic activation of the canonical wnt signaling pathway affects ectodermal patterning along the primary axis during larval development in the anthozoan Nematostella vectensis

Ectopic activation of the canonical wnt signaling pathway affects ectodermal patterning along the primary axis during larval development in the anthozoan Nematostella vectensis

Publication date: 15 August 2013
Source:Developmental Biology, Volume 380, Issue 2
Author(s): Heather Marlow , David Q. Matus , Mark Q. Martindale
The primary axis of cnidarians runs from the oral pole to the apical tuft and defines the major body axis of both the planula larva and adult polyp. In the anthozoan cnidarian Nematostella vectensis, the primary oral–aboral (O–Ab) axis first develops during the early embryonic stage. Here, we present evidence that pharmaceutical activators of canonical wnt signaling affect molecular patterning along the primary axis of Nematostella. Although not overtly morphologically complex, molecular investigations in Nematostella reveal that the O–Ab axis is demarcated by the expression of differentially localized signaling molecules and transcription factors that may serve roles in establishing distinct ectodermal domains. We have further characterized the larval epithelium by determining the position of a nested set of molecular boundaries, utilizing several newly characterized as well as previously reported epithelial markers along the primary axis. We have assayed shifts in their position in control embryos and in embryos treated with the pharmacological agents alsterpaullone and azakenpaullone, Gsk3β inhibitors that act as canonical wnt agonists, and the Wnt antagonist iCRT14, following gastrulation. Agonist drug treatments result in an absence of aboral markers, a shift in the expression boundaries of oral markers toward the aboral pole, and changes in the position of differentially localized populations of neurons in a dose-dependent manner, while antagonist treatment had the opposite effect. These experiments are consistent with canonical wnt signaling playing a role in an orally localized wnt signaling center. These findings suggest that in Nematostella, wnt signaling mediates O–Ab ectodermal patterning across a surprisingly complex epithelium in planula stages following gastrulation in addition to previously described roles for the wnt signaling pathway in endomesoderm specification during gastrulation and overall animal–vegetal patterning at earlier stages of anthozoan development.