Naum I. Gershenzon

Synergy of human Pol II core promoter elements revealed by statistical sequence analysis

MOTIVATION The subject of our paper is bioinformatics analysis of the distinguishing features of human promoter DNA sequences, in particular of synergetic combinations of core promoter elements therein. We suppose that specific scenarios of transcription initiation are essentially related to various particular implementations of the interaction of basal transcription machinery with promoter DNA, depending on the presence and mutual positioning of core promoter elements. RESULTS In addition to the combinations of core promoter elements previously experimentally confirmed [TATA box and Initiator (Inr), Downstream Promoter Element (DPE) and Inr, and TFIIB recognition element (BRE) and TATA box] we propose other alternate synergetic combinations: BRE and Inr, BRE and DPE, and TATA and DPE with respective models. The suggestion is based on a high statistical significance of the alternate combinations in promoters, comparable with the significance of the known combinations. We also present arguments that the BRE element is statistically more important than previously thought, and suggest possible mechanisms of action of the core elements in the promoters with multiple transcription start sites. CONTACT ioschikhes-1@medctr.osu.edu SUPPLEMENTARY INFORMATION Supplementary information is available at http://bmi.osu.edu/~ilya/synergy/Gershenzon_SuppMat-R.pdf.

Functional Characterization of Core Promoter Elements: the Downstream Core Element Is Recognized by TAF1

ABSTRACT Downstream elements are a newly appreciated class of core promoter elements of RNA polymerase II-transcribed genes. The downstream core element (DCE) was discovered in the human β-globin promoter, and its sequence composition is distinct from that of the downstream promoter element (DPE). We show here that the DCE is a bona fide core promoter element present in a large number of promoters and with high incidence in promoters containing a TATA motif. Database analysis indicates that the DCE is found in diverse promoters, supporting its functional relevance in a variety of promoter contexts. The DCE consists of three subelements, and DCE function is recapitulated in a TFIID-dependent manner. Subelement 3 can function independently of the other two and shows a TFIID requirement as well. UV photo-cross-linking results demonstrate that TAF1/TAFII250 interacts with the DCE subelement DNA in a sequence-dependent manner. These data show that downstream elements consist of at least two types, those of the DPE class and those of the DCE class; they function via different DNA sequences and interact with different transcription activation factors. Finally, these data argue that TFIID is, in fact, a core promoter recognition complex.

Theory of electrokinetic effects occurring at the final stage in the preparation of a tectonic earthquake

Crustal deformation processes occur with relative rapidity when short-term precursors appear at the final preparatory stage of a tectonic earthquake. This paper contains calculations of crustal bulk strain before an earthquake, based on the model of a rigid inclusion. The data give initial conditions for the problem of fluid percolation in a two-phase medium accompanied by electrokinetic effects. The solution provides a description of systems of currents arising in the vicinity of the source region. An analysis of this theoretical evidence yields information on the behaviour of short-term precursors in telluric currents and the geomagnetic field.

Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites

Position-weight matrices (PWMs) are broadly used to locate transcription factor binding sites in DNA sequences. The majority of existing PWMs provide a low level of both sensitivity and specificity. We present a new computational algorithm, a modification of the Staden–Bucher approach, that improves the PWM. We applied the proposed technique on the PWM of the GC-box, binding site for Sp1. The comparison of old and new PWMs shows that the latter increase both sensitivity and specificity. The statistical parameters of GC-box distribution in promoter regions and in the human genome, as well as in each chromosome, are presented. The majority of commonly used PWMs are the 4-row mononucleotide matrices, although 16-row dinucleotide matrices are known to be more informative. The algorithm efficiently determines the 16-row matrices and preliminary results show that such matrices provide better results than 4-row matrices.

Influence of small‐scale fluvial architecture on CO2 trapping processes in deep brine reservoirs

A number of important candidate CO2 reservoirs exhibit sedimentary architecture reflecting fluvial deposition. Recent studies have led to new conceptual and quantitative models for sedimentary architecture in fluvial deposits over a range of scales that are relevant to CO2 injection and storage. We used a geocellular modeling approach to represent this multiscaled and hierarchical sedimentary architecture. With this model, we investigated the dynamics of CO2 plumes, during and after injection, in such reservoirs. The physical mechanism of CO2 trapping by capillary trapping incorporates a number of related processes, i.e., residual trapping, trapping due to hysteresis of the relative permeability, and trapping due to hysteresis of the capillary pressure. Additionally, CO2 may be trapped due to differences in capillary entry pressure for different textural sedimentary facies (e.g., coarser-grained versus finer-grained cross sets). The amount of CO2 trapped by these processes depends upon a complex system of nonlinear and hysteretic characteristic relationships including how relative permeability and capillary pressure vary with brine and CO2 saturation. The results strongly suggest that representing small-scale features (decimeter to meter), including their organization within a hierarchy of larger-scale features, and representing their differences in characteristic relationships can all be critical to understanding trapping processes in some important candidate CO2 reservoirs.

Modeling of seismo-electromagnetic phenomena

A model for seismo-electromagnetic (SEM) phenomena is described. The electromagnetic signals generated by mechanical disturbances in the earths crust have been calculated and compared with reported seismo-electromagnetic signals (SEMS). The major known SEM phenomena, namely, tectonomagnetic variations, electrotelluric anomalies, geomagnetic variations in the ultra-low frequency range and electromagnetic emission in the radio frequency range, have been considered. We have calculated the spectral densities associated with various types of sources. The set of formulas necessary to calculate the detected (filtered and averaged) electric and magnetic fields generated by mechanical disturbances for a wide range of frequencies and at various distances from the source are presented. Based on these formulas, we discuss the conditions under which electrokinetic, piezomagnetic and piezolectric eects could be responsible for SEMS. A comparison of estimated values of SEMS with reported field measurements leads to the conclusion that the sources of most anomalous SEMS are relatively close to the detector. In other words, the source of the signal is local, although the source of the mechanical disturbance which activates it, i.e. the epicenter of an earthquake, may be far away. Recommendations for field experiments (appropriate detector sitting, detector parameters and frequency range) following from the model developed here are presented.

The features of Drosophila core promoters revealed by statistical analysis

BackgroundExperimental investigation of transcription is still a very labor- and time-consuming process. Only a few transcription initiation scenarios have been studied in detail. The mechanism of interaction between basal machinery and promoter, in particular core promoter elements, is not known for the majority of identified promoters. In this study, we reveal various transcription initiation mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters.ResultsUsing Drosophila-specific position-weight matrices, we identified promoters containing TATA box, Initiator, Downstream Promoter Element (DPE), and Motif Ten Element (MTE), as well as core elements discovered in Human (TFIIB Recognition Element (BRE) and Downstream Core Element (DCE)). Promoters utilizing known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE, and DPE_MTE) were identified. We also establish the existence of promoters with potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis revealed several motifs with the features of promoter elements, including possible novel core promoter element(s). Comparison of Human and Drosophila showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic combinations thereof, as well as most of the same functional and mutual positions of the core elements. No statistical evidence of MTE utilization in Human was found. Distinct nucleosome positioning in particular promoter classes was revealed.ConclusionWe present lists of promoters that potentially utilize the aforementioned elements/combinations. The number of these promoters is two orders of magnitude larger than the number of promoters in which transcription initiation was experimentally studied. The sequences are ready to be experimentally tested or used for further statistical analysis. The developed approach may be utilized for other species.

Linear Phase Slope in Pulse Design: Application to Coherence Transfer

Using optimal control methods, robust broadband excitation pulses can be designed with a defined linear phase dispersion. Applications include increased bandwidth for a given pulse length compared to equivalent pulses requiring no phase correction, selective pulses, and pulses that mitigate the effects of relaxation. This also makes it possible to create pulses that are equivalent to ideal hard pulses followed by an effective evolution period. For example, in applications, where the excitation pulse is followed by a constant delay, e.g. for the evolution of heteronuclear couplings, part of the pulse duration can be absorbed in existing delays, significantly reducing the time overhead of long, highly robust pulses. We refer to the class of such excitation pulses with a defined linear phase dispersion as ICEBERG pulses (Inherent Coherence Evolution optimized Broadband Excitation Resulting in constant phase Gradients). A systematic study of the dependence of the excitation efficiency on the phase dispersion of the excitation pulses is presented, which reveals surprising opportunities for improved pulse sequence performance.

Modelling the Connection Between Earthquake Preparation Processes and Crustal Electromagnetic Emission

Abstract The steadily increasing amount of information available today on the natural electromagnetic emission (EME) of the radio frequency band associated with seismic events raises the problem of the origin of this phenomenon. A natural hypothesis is that EME is due to earthquake preparation processes. The present paper is concerned with substantiating a model that postulates EME to be caused by cracking of surficial crustal layers in the zone of earthquake preparation. The crust is assumed to have ordered hierarchical structure. Individual elements of that structure are formed of blocks of different scales and obey principles of similarity. Between the blocks are soft interlayers with a finite strength limit. A regular periodic structure with a cubic lattice is studied. As a result, EME intensity as a function of magnitude is evaluated. Methodological recommendations are given for organization of field observations of EME in relation to earthquake prediction.

On the electromagnetic field of an earthquake focus

Abstract Several mechanoelectromagnetic effects are analysed as probable generating mechanisms of electromagnetic impulses produced by an earthquake in its focus. Based on a simple mechanical concept of earthquakes and well-known theories of electrokinetic, piezomagnetic and induction effects, a dipole model of an earthquake-driven electromagnetic source is developed. Corresponding electric and/or magnetic dipole moment values are calculated as functions of earthquake focus parameters and generating mechanisms and are used to estimate the field intensities observable on the surface at different distances from an epicenter of an earthquake of a given magnitude ( M ). Calculated field values are compared with observational data.