Extending the Code of Sequence Readout by Gene Regulatory Proteins: The Role of Hoogsteen Base Pairing in p53-DNA Recognition

Abstract Summary The sequence specific recognition of DNA by regulatory proteins typically occurs by establishing hydrogen bonds and non-bonded contacts between chemical sub-structures of nucleotides and amino acids forming the compatible interacting surfaces. The recognition process is also influenced by the physicochemical and conformational character of the target oligonucleotide motif. Although the role of these mechanisms in DNA-protein interactions is well-established, bioinformatical methods rarely address them directly, instead binding specificity is mostly assessed at nucleotide level. DNA Readout Viewer (DRV) aims to provide a novel DNA representation, facilitating in-depth view into these mechanisms by the concurrent visualization of functional groups and a diverse collection of DNA descriptors. By applying its intuitive representation concept for various DNA recognition related visualization tasks, DRV can contribute to unravelling the binding specificity factors of DNA-protein interactions. Availability and implementation DRV is freely available at https://drv.brc.hu. Supplementary information Supplementary data are available at Bioinformatics online.

Download Full-text

Sequence dependence of transient Hoogsteen base-pairing in DNA

10.1101/2021.08.04.454872 ◽

2021 ◽

Author(s):

Alberto Pérez de Alba Ortíz ◽

Jocelyne Vreede ◽

Bernd Ensing

Keyword(s):

Dynamic Equilibrium ◽

Double Helix ◽

Free Energy Calculations ◽

Dominant Factor ◽

Base Pairing ◽

Sequence Dependence ◽

Purine Base ◽

Sequence Variations ◽

Hoogsteen Base Pairing

Hoogsteen (HG) base-pairing is characterized by a 180° rotation of the purine base with respect to the Watson-Crick-Franklin (WCF) motif. Recently, it has been found that both conformations coexist in a dynamical equilibrium and that several biological functions require HG pairs. This relevance has motivated experimental and computational investigations of the base-pairing transition. However, a systematic simulation of sequence variations has remained out of reach. Here, we employ advanced path-based methods to perform unprecedented free-energy calculations. Our methodology enables us to study the different mechanisms of purine rotation, either remaining inside or after flipping outside of the double helix. We study seven different sequences, which are neighbor variations of a well-studied A·T pair in A6-DNA. We observe the known effect of A·T steps favoring HG stability, and find evidence of triple-hydrogen-bonded neighbors hindering the inside transition. More importantly, we identify a dominant factor: the direction of the A rotation, with the 6-ring pointing either towards the longer or shorter segment of the chain, respectively relating to a lower or higher barrier. This highlights the role of DNA's relative flexibility as a modulator of the WCF/HG dynamic equilibrium. Additionally, we provide a robust methodology for future HG proclivity studies.

Download Full-text

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Download Full-text

1139: The Predictive Role of Clinicopathological Parameters and Cell Cycle Regulatory Proteins (P53, Kl67 AND BCL-2) in Biochemical Relapse After Radical Prostatectomy (RP) in Intermediate and High Risk Group. A Tissue Microarray Study

The Journal of Urology ◽

10.1016/s0022-5347(18)31353-3 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 376-376

Author(s):

Barbaros A. Baseskioglu ◽

Dilek E. Baydar ◽

Bülent Akduman ◽

Sertac Yazici ◽

Angelo M. DeMarzo ◽

...

Keyword(s):

Risk Group ◽

High Risk Group ◽

Regulatory Proteins ◽

Clinicopathological Parameters ◽

Biochemical Relapse ◽

Microarray Study ◽

Cell Cycle Regulatory Proteins ◽

Group A ◽

Predictive Role

Download Full-text

The Gene Regulatory Roles of Herbal Extracts on the Growth, Immune System, and Reproduction of Fish

Animals ◽

10.3390/ani11082167 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2167

Author(s):

Ehsan Ahmadifar ◽

Hamideh Pourmohammadi Fallah ◽

Morteza Yousefi ◽

Mahmoud A. O. Dawood ◽

Seyed Hossein Hoseinifar ◽

...

Keyword(s):

Immune System ◽

Mode Of Action ◽

Medicinal Herbs ◽

Environmental Stressors ◽

Fish Diet ◽

Sustainable Aquaculture ◽

Herbal Supplements ◽

Aquatic Animals ◽

Gene Regulatory

The crucial need for safe and healthy aquatic animals obligates researchers in aquaculture to investigate alternative and beneficial additives. Medicinal herbals and their extracts are compromised with diverse effects on the performances of aquatic animals. These compounds can affect growth performance and stimulate the immune system when used in fish diet. In addition, the use of medicinal herbs and their extracts can reduce oxidative stress induced by several stressors during fish culture. Correspondingly, aquatic animals could gain increased resistance against infectious pathogens and environmental stressors. Nevertheless, the exact mode of action where these additives can affect aquatic animals’ performances is still not well documented. Understanding the mechanistic role of herbal supplements and their derivatives is a vital tool to develop further the strategies and application of these additives for feasible and sustainable aquaculture. Gene-related studies have clarified the detailed information on the herbal supplements’ mode of action when administered orally in aquafeed. Several review articles have presented the potential roles of medicinal herbs on the performances of aquatic animals. However, this review article discusses the outputs of studies conducted on aquatic animals fed dietary, medicinal herbs, focusing on the gene expression related to growth and immune performances. Furthermore, a particular focus is directed to the expected influence of herbal supplements on the reproduction of aquatic animals.

Download Full-text

Peroxiredoxins as Potential Targets for Cardiovascular Disease

Antioxidants ◽

10.3390/antiox10081244 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1244

Author(s):

Se-Jin Jeong ◽

Jong-Gil Park ◽

Goo Taeg Oh

Keyword(s):

Cardiovascular Disease ◽

Intracellular Signaling ◽

Toxic Substance ◽

Regulatory Proteins ◽

The Past ◽

Glutathione Peroxidases ◽

Intracellular Signals ◽

Common Etiology ◽

Cardiovascular Cells

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Hydrogen peroxide (H2O2), as an endogenous ROS in aerobic cells, is a toxic substance that can induce OS. However, many studies conducted over the past two decades have provided substantial evidence that H2O2 acts as a diffusible intracellular signaling messenger. Antioxidant enzymes, including superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins (Prdxs), maintain the balance of ROS levels against augmentation of ROS production during the pathogenesis of CVD. Especially, Prdxs are regulatory sensors of transduced intracellular signals. The intracellular abundance of Prdxs that specifically react with H2O2 act as regulatory proteins. In this review, we focus on the role of Prdxs in the regulation of ROS-induced pathological changes in the development of CVD.

Download Full-text