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Trends in Genetics: TIG

Arthur L Beaudet
What might be the benefits of whole-genome rather than whole-exome sequencing (WES) for identifying the genetic causes of human disabilities? A recent paper by Doan et al. focuses attention on mutations in human accelerated regions (HARs), a subset of genomic regulatory elements showing accelerated evolution between chimpanzees and humans.
November 28, 2016: Trends in Genetics: TIG
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
November 23, 2016: Trends in Genetics: TIG
Mingyu Li, Liyuan Zhao, Patrick S Page-McCaw, Wenbiao Chen
Geneticists have long sought the ability to manipulate vertebrate genomes by directly altering the information encoded in specific genes. The recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease has the ability to bind single loci within vertebrate genomes and generate double-strand breaks (DSBs) at those sites. These DSBs induce an endogenous DSB repair response that results in small insertions or deletions at the targeted site. Alternatively, a template can be supplied, in which case homology-directed repair results in the generation of engineered alleles at the break site...
December 2016: Trends in Genetics: TIG
Rico Schieweck, Bastian Popper, Michael A Kiebler
Local protein expression at synapses is a prerequisite for learning in mammalian neurons. It has been shown that a subset of RNAs is localized in dendrites. These transcripts are first assembled into ribonucleoprotein particles in the cell body and are then transported along the cytoskeleton to or near synapses in a translationally repressed state. However, we know very little about the underlying mechanisms of local translation as well as potential protein degradation. Research in the last years showed many features of general translation...
December 2016: Trends in Genetics: TIG
Muhammad A Zabidi, Alexander Stark
Gene expression is regulated by genomic enhancers that recruit transcription factors and cofactors to activate transcription from target core promoters. Over the past years, thousands of enhancers and core promoters in animal genomes have been annotated, and we have learned much about the domain structure in which regulatory genomes are organized in animals. Enhancer-core-promoter targeting occurs at several levels, including regulatory domains, DNA accessibility, and sequence-encoded core-promoter specificities that are likely mediated by different regulatory proteins...
December 2016: Trends in Genetics: TIG
Hironori Hojo, Andrew P McMahon, Shinsuke Ohba
Skeletal development creates the physical framework that shapes our body and its actions. In the past two decades, genetic studies have provided important insights into the molecular processes at play, including the roles of signaling pathways and transcriptional effectors that coordinate an orderly, progressive emergence and expansion of distinct cartilage and bone cell fates in an invariant temporal and spatial pattern for any given skeletal element within that specific vertebrate species. Genome-scale studies have provided additional layers of understanding, moving from individual genes to the gene regulatory landscape, integrating regulatory information through cis-regulatory modules into cell type-specific gene regulatory programs...
December 2016: Trends in Genetics: TIG
Yang Wang, Jing Crystal Zhao
Eukaryotic mRNA undergoes chemical modification both at the 5' cap and internally. Among internal modifications, N(6)-methyladensone (m(6)A), by far the most abundant, is present in all eukaryotes examined so far, including mammals, flies, plants, and yeast. m(6)A modification has an essential role in diverse biological processes. Over the past few years, our knowledge relevant to the establishment and function of this modification has grown rapidly. In this review, we focus on technologies that have facilitated m(6)A detection in mRNAs, the identification of m(6)A methylation enzymes and binding proteins, and potential functions of the modification at the molecular level...
December 2016: Trends in Genetics: TIG
Frédéric Chédin
RNA molecules, such as long noncoding RNAs (lncRNAs), have critical roles in regulating gene expression, chromosome architecture, and the modification states of chromatin. Recent developments suggest that RNA also influences gene expression and chromatin patterns through the interaction of nascent transcripts with their DNA template via the formation of co-transcriptional R-loop structures. R-loop formation over specific, conserved, hotspots occurs at thousands of genes in mammalian genomes and represents an important and dynamic feature of mammalian chromatin...
December 2016: Trends in Genetics: TIG
Michael R Brent
One of the principal mechanisms by which cells differentiate and respond to changes in external signals or conditions is by changing the activity levels of transcription factors (TFs). This changes the transcription rates of target genes via the cell's TF network, which ultimately contributes to reconfiguring cellular state. Since microarrays provided our first window into global cellular state, computational biologists have eagerly attacked the problem of mapping TF networks, a key part of the cell's control circuitry...
November 2016: Trends in Genetics: TIG
Christopher E Slagle, Frank L Conlon
Congenital heart defects remain a leading cause of infant mortality in the western world, despite decades of research focusing on cardiovascular development and disease. With the recent emergence of several high-throughput technologies including RNA sequencing, chromatin-immunoprecipitation-coupled sequencing, mass-spectrometry-based proteomics analyses, and the numerous variations of these strategies, investigations into cardiac development have been transformed from candidate-based studies into whole-genome, -transcriptome, and -proteome undertakings...
November 2016: Trends in Genetics: TIG
Steven W Criscione, Yee Voan Teo, Nicola Neretti
Cellular senescence, an irreversible growth arrest triggered by a variety of stressors, plays important roles in normal physiology and tumor suppression, but accumulation of senescent cells with age contributes to the functional decline of tissues. Senescent cells undergo dramatic alterations to their chromatin landscape that affect genome accessibility and their transcriptional program. These include the loss of DNA-nuclear lamina interactions, the distension of centromeres, and changes in chromatin composition that can lead to the activation of retrotransposons...
November 2016: Trends in Genetics: TIG
Volker Boehm, Niels H Gehring
The exon junction complex (EJC) is an RNA-binding protein complex that is assembled and deposited onto mRNAs during splicing. The EJC comprises four core components that bind to not only canonical sites upstream of exon-exon junctions, but also to noncanonical sites at other positions in exons. EJC-associated proteins are recruited by the EJC at different steps of gene expression to execute the multiple functions of the EJC. Recently, new insights have been obtained into how EJCs stimulate pre-mRNA splicing, and mRNA export, translation, and degradation...
November 2016: Trends in Genetics: TIG
Anne-Laure Valton, Marie-Noëlle Prioleau
DNA replication is a highly regulated process that ensures the correct duplication of the genome at each cell cycle. A precise cell type-specific temporal program controls the duplication of complex vertebrate genomes in an orderly manner. This program is based on the regulation of both replication origin firing and replication fork progression. G-quadruplexes (G4s), DNA secondary structures displaying noncanonical Watson-Crick base pairing, have recently emerged as key controllers of genome duplication. Here we discuss the various means by which G4s affect this fundamental cellular process...
November 2016: Trends in Genetics: TIG
Jessica K Tyler
To carry epigenetic information, the chromatin structure must be accurately rebuilt after its deconstruction during genomic replication. Using an elegant, novel approach, Vasseur et al.[1] reveal that transcription plays a key role in sculpting the chromatin after DNA replication.
November 2016: Trends in Genetics: TIG
Ray Ming, Ching Man Wai, Romain Guyot
Pineapple occupies an important phylogenetic position and its reference genome expedites genomic research within the family Bromeliaceae and more widely among monocots. One such research focus is the evolution of crassulacean acid metabolism (CAM) photosynthesis. Acquiring circadian clock cis-regulatory elements in CAM-related genes might be a critical step in the evolution of this form of photosynthesis. Follow-up studies will clarify the processes and evolutionary forces leading to the multiple independent origins of CAM photosynthesis within the family Bromeliaceae and in over 400 genera across 36 families...
November 2016: Trends in Genetics: TIG
Ying-Hsin Chen, Jeff Coller
Precise elimination of maternal mRNAs plays a critical role during the maternal-to-zygotic transition (MZT) to promote developmental processing. Two new studies demonstrate that, in eukaryotes, codon-mediated decay is a conserved mechanism to shape maternal mRNA stability by affecting deadenylation rate in a translation-dependent manner. These studies add to a growing body of literature suggesting that translational elongation rates are a major determinant of mRNA stability.
November 2016: Trends in Genetics: TIG
Raz Bar-Ziv, Yoav Voichek, Naama Barkai
DNA replication perturbs the dosage balance between genes that replicate early during S phase and those that replicate late. If propagated to influence protein content, this dosage imbalance could influence cellular functions. In bacteria, mechanisms have evolved to use this imbalance to tune certain processes with the rate of cell growth. By contrast, eukaryotes buffer this dosage imbalance to ensure gene expression homeostasis also during S phase. Here, we outline classical and more recent studies describing how different organisms deal with this replication-dependent dosage imbalance, and describe recent results linking the eukaryotic buffering mechanism to replication-dependent histone acetylation...
November 2016: Trends in Genetics: TIG
Kayla Viets, Kiara C Eldred, Robert J Johnston
Across the animal kingdom, visual systems have evolved to be uniquely suited to the environments and behavioral patterns of different species. Visual acuity and color perception depend on the distribution of photoreceptor (PR) subtypes within the retina. Retinal mosaics can be organized into three broad categories: stochastic/regionalized, regionalized, and ordered. We describe here the retinal mosaics of flies, zebrafish, chickens, mice, and humans, and the gene regulatory networks controlling proper PR specification in each...
October 2016: Trends in Genetics: TIG
Afsoon Saadin, Michelle Starz-Gaiano
Drosophila border cells undergo a straightforward and stereotypical collective migration during egg development. However, a complex genetic program underlies this process. A variety of approaches, including biochemical, genetic, and imaging strategies have identified many regulatory components, revealing layers of control. This complexity suggests that the active processes of evaluating the environment, remodeling the cytoskeleton, and coordinating movements among cells, demand rapid systems for modulating cell behaviors...
October 2016: Trends in Genetics: TIG
He Huang, Dmitri A Nusinow
In Arabidopsis thaliana an assembly of proteins named the evening complex (EC) has been established as an essential component of the circadian clock with conserved functions in regulating plant growth and development. Recent studies identifying EC-regulated genes and EC-interacting proteins have expanded our understanding of EC function. In this review we focus on new progress uncovering how the EC contributes to the circadian network through the integration of environmental inputs and the direct regulation of key clock genes...
October 2016: Trends in Genetics: TIG
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