Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor

Neurogenesis, and the processes through which neural stem cells and progenitor cells differentiate into neurons, occurs most actively during embryonic development, although neural differentiation continues at lower levels in certain brain regions well into adulthood. A vast regulatory network involving many known and conserved transcription factors regulates these functions. We have identified a novel zinc finger transcription factor (TF), ZNF286A, which is conserved in all eutherians and marsupials and provide evidence that this novel TF plays a role in regulation of mammalian neurogenesis. ZNF286 occurs as a unique gene in most species. However, we demonstrate evidence that a gene duplication event in very recent primate history created a human-specific duplicate of ZNF286A, called ZNF286B. ZNF286B arose as part of a larger duplication in human chromosome 17, approximately 600,000 kb in length, that also includes many surrounding genes. Concomitant with (or shortly after) duplication, a processed and incomplete FOXO3B pseudo-gene was inserted into the ZNF286B genomic sequence and a DNA segment, encompassing a coding exon and regulatory sequences present in the ancestral ZNF286A gene, was deleted. As a result, ZNF286B encodes a protein with significant structural and expression differences relative to the ancestral gene. Most strikingly, the exon deleted in ZNF286B codes for the chromatin-interacting KRAB-domains that are present in the ZNF286A gene; in this respect the new human paralog resembles a natural KRAB-less alternative isoform that we demonstrate to be expressed naturally from the parental ZNF286A gene. Using ChIP and siRNA knockdown, we show that ZNF286A protein binds to DNA at or near genes involved in the networks controlling the differentiation of neurons and the formation of axons during neurogenesis, and that both ZNF286A and ZNF286B directly regulate expression of many of those same genes. The pattern of DNA binding closely parallels binding of well-known neuronal differentiation factor, REST, in the same cell lines; siRNA results suggest that ZNF286 proteins act antagonistically to REST during development. We show that the mouse gene, Zfp286, is expressed at high levels in the developing nervous system and that both mouse and human genes and proteins are up-regulated transiently over the course of neurogenic differentiation in vitro, consistent with the predicted biological role. We hypothesize that the duplication event that gave rise to ZNF286B allowed for independent regulation of the KRAB-less isoform of the ZNF286 protein, permitting this ancient mammalian gene to take on novel functions in the adult human brain

Isolation and characterization of microsatellite loci from two inbreeding bark beetle species (Coccotrypes)

We developed 14 microsatellite markers in Coccotrypes carpophagus and 14 in C. dactyliperda. These loci will be used for studying genetic structure and the level of inbreeding in populations in the Canary Islands and Madeira. As a result of long-term inbreeding, genetic variability is relatively low in these bark beetle species. We found one to five alleles per locus in 29 C. carpophagus and 41 C. dactyliperda from various localities. Eleven of the markers developed for C. carpophagus amplified in C. dactyliperda and seven of the markers developed for C. dactyliperda amplified in C. carpophagus

NOBAI: a web server for character coding of geometrical and statistical features in RNA structure

The Numeration of Objects in Biology: Alignment Inferences (NOBAI) web server provides a web interface to the applications in the NOBAI software package. This software codes topological and thermodynamic information related to the secondary structure of RNA molecules as multi-state phylogenetic characters, builds character matrices directly in NEXUS format and provides sequence randomization options. The web server is an effective tool that facilitates the search for evolutionary history embedded in the structure of functional RNA molecules. The NOBAI web server is accessible at ‘http://www.manet.uiuc.edu/nobai/nobai.php’. This web site is free and open to all users and there is no login requirement

Author Correction: Mitonuclear incompatibility as a hidden driver behind the genome ancestry of African admixed cattle

The original article contained minor errors in Figs. 1 and 3 which have both since been corrected

DAhunter: a web-based server that identifies homologous proteins by comparing domain architecture

We present DAhunter, a web-based server that identifies homologous proteins by comparing domain architectures, the organization of protein domains. A major obstacle in comparison of domain architecture is the existence of ‘promiscuous’ domains, which carry out auxiliary functions and appear in many unrelated proteins. To distinguish these promiscuous domains from protein domains, we assigned a weight score to each domain extracted from RefSeq proteins, based on its abundance and versatility. A domain's score represents its importance in the ‘protein world’ and is used in the comparison of domain architectures. In scoring domains, DAhunter also considers domain combinations as well as single domains. To measure the similarity of two domain architectures, we developed several methods that are based on algorithms used in information retrieval (the cosine similarity, the Goodman–Kruskal γ function, and domain duplication index) and then combined these into a similarity score. Compared with other domain architecture algorithms, DAhunter is better at identifying homology. The server is available at http://www.dahunter.kr and http://localodom.kobic.re.kr/dahunter/index.ht

Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice

Agonistic encounters are powerful effectors of future behavior, and the ability to learn from this type of social challenge is an essential adaptive trait. We recently identified a conserved transcriptional program defining the response to social challenge across animal species, highly enriched in transcription factor (TF), energy metabolism, and developmental signaling genes. To understand the trajectory of this program and to uncover the most important regulatory influences controlling this response, we integrated gene expression data with the chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged mice over time. The expression data revealed a complex spatiotemporal patterning of events starting with neural signaling molecules in the frontal cortex and ending in the modulation of developmental factors in the amygdala and hypothalamus, underpinned by a systems-wide shift in expression of energy metabolism-related genes. The transcriptional signals were correlated with significant shifts in chromatin accessibility and a network of challenge-associated TFs. Among these, the conserved metabolic and developmental regulator ESRRA was highlighted for an especially early and important regulatory role. Cell-type deconvolution analysis attributed the differential metabolic and developmental signals in this social context primarily to oligodendrocytes and neurons, respectively, and we show that ESRRA is expressed in both cell types. Localizing ESRRA binding sites in cortical chromatin, we show that this nuclear receptor binds both differentially expressed energy-related and neurodevelopmental TF genes. These data link metabolic and neurodevelopmental signali ng to social challenge, and identify key regulatory drivers of this process with unprecedented tissue and temporal resolution

Mutations in two global regulators lower individual mortality in Escherichia coli

There has been considerable investigation into the survival of bacterial cells under stress conditions, but little is known about the causes of mortality in the absence of exogenous stress. That there is a basal frequency of cell death in such populations may reflect that it is either impossible to avoid all lethal events, or alternatively, that it is too costly. Here, through a genetic screen in the model organism Escherichia coli, we identify two mutants with lower frequencies of mortality: rssB and fliA. Intriguingly, these two genes both affect the levels of different sigma factors within the cell. The rssB mutant displays enhanced resistance to multiple external stresses, possibly indicating that the cell gains its increased vitality through elevated resistance to spontaneous, endogenous stresses. The loss of fliA does not result in elevated stress resistance; rather, its survival is apparently due to a decreased physical stress linked to the insertion of the flagellum through the membrane and energy saved through the loss of the motor proteins. The identification of these two mutants implies that reducing mortality is not impossible; rather, due to its cost, it is subject to trade-offs with other traits that contribute to the competitive success of the organism