This volume contains cutting-edge techniques to study the function of enhancers and promoters in depth. Chapters are divided into six sections and describe enhancer-promoter transcripts, nucleosome occupancy, DNA accessibility, chromatin interactions, protein-DNA interactions, functional analyses, and DNA methylation assays. Written in the Methods in Molecular Biology series format, chapters include comprehensive introductions, lists of the necessary materials and reagents, step-by-step laboratory protocols, and useful suggestions for troubleshooting. Authoritative and cutting-edge, Enhancers and Promoters: Methods and Protocols is a useful guide for future experiments.

Nuclear Architecture and Dynamics provides a definitive resource for (bio)physicists and molecular and cellular biologists whose research involves an understanding of the organization of the genome and the mechanisms of its proper reading, maintenance, and replication by the cell. This book brings together the biochemical and physical characteristics of genome organization, providing a relevant framework in which to interpret the control of gene expression and cell differentiation. It includes work from a group of international experts, including biologists, physicists, mathematicians, and bioinformaticians who have come together for a comprehensive presentation of the current developments in the nuclear dynamics and architecture field. The book provides the uninitiated with an entry point to a highly dynamic, but complex issue, and the expert with an opportunity to have a fresh look at the viewpoints advocated by researchers from different disciplines. - Highlights the link between the (bio)chemistry and the (bio)physics of chromatin - Deciphers the complex interplay between numerous biochemical factors at task in the nucleus and the physical state of chromatin - Provides a collective view of the field by a large, diverse group of authors with both physics and biology backgrounds

The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.

It is said that "necessity is the mother of invention". To be sure, wheels and pulleys were invented out of necessity by the tenacious minds of upright citi zens. Looking at the history of mankind, however, one has to add that "Ieisure is the mother of cultural improvement". Man's creative genius flourished only when his mind, freed from the worry of daily toils, was permitted to entertain apparently useless thoughts. In the same manner, one might say with regard to evolution that "natural selection mere(y tnodifted, while redundanry created". Natural selection has been extremely effective in policing alleHe mutations which arise in already existing gene loci. Because of natural selection, organisms have been able to adapt to changing environments, and by adaptive radiation many new species were created from a common ancestral form. Y et, being an effective policeman, natural selection is extremely conservative by nature. Had evolution been entirely dependent upon natural selection, from a bacterium only numerous forms of bacteria would have emerged. The creation of metazoans, vertebrates and finally mammals from unicellular organisms would have been quite impos sible, for such big leaps in evolution required the creation of new gene loci with previously nonexistent functions. Only the cistron which became redun dant was able to escape from the relentless pressure of natural selection, and by escaping, it accumulated formerly forbidden mutations to emerge as a new gene locus.

Computational Genomics with R provides a starting point for beginners in genomic data analysis and also guides more advanced practitioners to sophisticated data analysis techniques in genomics. The book covers topics from R programming, to machine learning and statistics, to the latest genomic data analysis techniques. The text provides accessible information and explanations, always with the genomics context in the background. This also contains practical and well-documented examples in R so readers can analyze their data by simply reusing the code presented. As the field of computational genomics is interdisciplinary, it requires different starting points for people with different backgrounds. For example, a biologist might skip sections on basic genome biology and start with R programming, whereas a computer scientist might want to start with genome biology. After reading: You will have the basics of R and be able to dive right into specialized uses of R for computational genomics such as using Bioconductor packages. You will be familiar with statistics, supervised and unsupervised learning techniques that are important in data modeling, and exploratory analysis of high-dimensional data. You will understand genomic intervals and operations on them that are used for tasks such as aligned read counting and genomic feature annotation. You will know the basics of processing and quality checking high-throughput sequencing data. You will be able to do sequence analysis, such as calculating GC content for parts of a genome or finding transcription factor binding sites. You will know about visualization techniques used in genomics, such as heatmaps, meta-gene plots, and genomic track visualization. You will be familiar with analysis of different high-throughput sequencing data sets, such as RNA-seq, ChIP-seq, and BS-seq. You will know basic techniques for integrating and interpreting multi-omics datasets. Altuna Akalin is a group leader and head of the Bioinformatics and Omics Data Science Platform at the Berlin Institute of Medical Systems Biology, Max Delbrück Center, Berlin. He has been developing computational methods for analyzing and integrating large-scale genomics data sets since 2002. He has published an extensive body of work in this area. The framework for this book grew out of the yearly computational genomics courses he has been organizing and teaching since 2015.

In Gene Regulatory Sequences and Human Disease, the Editor will introduce the different technological advances that led to this breakthrough. In addition, several examples will be provided of nucleotide variants in noncoding sequences that have been shown to be associated with various human diseases.

Chromatin Regulation and Dynamics integrates knowledge on the dynamic regulation of primary chromatin fiber with the 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes. The final chapters discuss the many ways chromatin dynamics can synergize to fundamentally contribute to the development of complex diseases. Chromatin dynamics, which is strategically positioned at the gene-environment interface, is at the core of disease development. As such, Chromatin Regulation and Dynamics, part of the Translational Epigenetics series, facilitates the flow of information between research areas such as chromatin regulation, developmental biology, and epidemiology by focusing on recent findings of the fast-moving field of chromatin regulation. - Presents and discusses novel principles of chromatin regulation and dynamics with a cross-disciplinary perspective - Promotes crosstalk between basic sciences and their applications in medicine - Provides a framework for future studies on complex diseases by integrating various aspects of chromatin biology with cellular metabolic states, with an emphasis on the dynamic nature of chromatin and stochastic principles - Integrates knowledge on the dynamic regulation of primary chromatin fiber with 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes