Preface

In accordance with progress in genome informatics, developments in molecular biology have greatly changed medical sciences. For example, diagnosis of certain diseases, including cancer, could be carried out by genome analysis, which accurately shows every mutated nucleotide in individual genomes. Moreover, genome editing technologies are expected to be clinically applied on some diseases, such as Duchenne muscular dystrophy. Recent studies revealed that specific human diseases are frequently accompanied with dysregulation in transcription or gene expression. In this regard, understanding mechanisms of the transcription system is essential for development in medical and life sciences. This will direct us as to how we could apply gene expression control for practical uses, not only in diagnosis and therapeutics but also in industrial production of recombinant cytokines, antibodies, and hormones.

In Section 1 of this book, pathologically important roles of the transcriptional regulation are described. Inner cellular signalling pathway plays important roles in the regulation of various cellular behaviours.

In Section 2, Chapter 2 discusses in detail how MAPK induced signals affect transcriptional initiation, elongation, and termination. The studies in MAPK-mediated transcriptional controlling system will contribute to novel therapeutics for cancer, immunological and metabolic diseases. Not only cell surviving or proliferationcausing signals, but also dysregulation in autophagy could play causative roles in generation of cancer and neurodegenerative diseases. In Chapter 3, the possible relationships between expression of the autophagy associated factor-encoding genes and nicotinic acetylcholine receptors are discussed. In Chapter 4, we explain dysregulated transcription in odontogenic cysts. The author discusses if the overexpressed genes, including *PTCH*, or their encoding proteins could be the right targets for medical treatment.

In Section 3, we look over transcriptional control. Current advances in molecular biology enabled accumulation of data from genomic, transcriptomic, and proteomic analyses. In Chapter 5, we learn how to utilize and apply such data on the examination of the transcriptional control system. The author performed datamining from ChIP-seq analyses to discuss the transcriptional control of urea-cycle factor encoding gene expression. If scientists find some key transcription factors, they might be applied on gene-therapy. In Chapter 6, the authors argue for the gene delivery system, which enables pin-point therapeutics on pathological tissue. The transcriptional control is not only applied for medical subjects, but also with food supply. In Chapter 7, the author presents a platform to discuss nutrigenomics, which will contribute to increase the production rate of meat and milk. The concept might be relevant to prevention of diseases, including diabetes and aging-associated syndromes.

Although applications of the transcriptional control on life sciences are making rapid progress, basic study is necessary for further progress toward a new era

**II**

**Chapter 7 121**

Basic Studies in Transcription Toward a New Era of Molecular Biology **149**

**Chapter 8 151**

**Chapter 9 167**

Transcriptional Initiation in Ribosomal Protein Genes in the Fission Yeast

Gene Regulation in Ruminants: A Nutritional Perspective

*by Diego A. Rojas, Sandra Moreira-Ramos, Fabiola Urbina* 

*by Sally Wang, Gregory F. Payne and William E. Bentley*

Repurposing *E. coli* by Engineering Quorum Sensing and Redox

*by Johan S. Osorio and Sonia J. Moisa*

*Schizosaccharomyces pombe*

*and Edio Maldonado*

Genetic Circuits

**Section 4**

of molecular biology. In Section 4, transcriptional control in microorganisms is reviewed. In Chapter 8, authors successfully review the transcription initiation in ribosomal protein-encoding genes in yeast cells. The concept encourages focus on transcription from TATA-less promoters to overview landscapes of the *Central Dogma*. In prokaryotic cells, quorum sensing plays a role in regulation of cell-cell communication system by affecting transcription. In Chapter 9, authors faithfully address the mechanisms of how environmental signals control gene expression in prokaryotic cells.

"Examine thoroughly not only enemies but also ourselves, and we will win every battle." This is a saying from a general in ancient China. Now, what are the enemies? Molecular biologists who are studying transcriptional systems might define them as human diseases or problems/difficulties in producing recombinant proteins. Now, based on the scientific discussion, we are reaching the point to look over life on earth. In the near future, artificial intelligence (AI) will be applied not only to basic studies but also to clinical purposes. We should always be aware what science is aiming for.

> **Fumiaki Uchiumi, Ph.D.** Professor, Department of Gene Regulation, Tokyo University of Science, Japan

> > **1**

Section 1

Introduction

Section 1 Introduction

**IV**

prokaryotic cells.

is aiming for.

of molecular biology. In Section 4, transcriptional control in microorganisms is reviewed. In Chapter 8, authors successfully review the transcription initiation in ribosomal protein-encoding genes in yeast cells. The concept encourages focus on transcription from TATA-less promoters to overview landscapes of the *Central Dogma*. In prokaryotic cells, quorum sensing plays a role in regulation of cell-cell communication system by affecting transcription. In Chapter 9, authors faithfully address the mechanisms of how environmental signals control gene expression in

"Examine thoroughly not only enemies but also ourselves, and we will win every battle." This is a saying from a general in ancient China. Now, what are the enemies? Molecular biologists who are studying transcriptional systems might define them as human diseases or problems/difficulties in producing recombinant proteins. Now, based on the scientific discussion, we are reaching the point to look over life on earth. In the near future, artificial intelligence (AI) will be applied not only to basic studies but also to clinical purposes. We should always be aware what science

**Fumiaki Uchiumi, Ph.D.**

Japan

Tokyo University of Science,

Professor, Department of Gene Regulation,

**3**

**Chapter 1**

Sciences

**1. Introduction**

human diseases.

Introductory Chapter: Gene

*Fumiaki Uchiumi and Masashi Asai*

**2. Transcription factors (TFs) in mammalian cells**

sequence-specific binding proteins.

**2.1 The GTFs and TATA-less promoters**

Expression Controlling System

and Its Application to Medical

We have learned that genes in mammalian cells are transcribed into messenger RNAs (mRNAs), which are to be translated into polypeptides (proteins). This is known as "Central Dogma." Gene expression must be appropriately maintained to regulate development, differentiation, and proliferation of cells. Imbalances or disturbances in gene expression are sometimes deleterious for living things. For example, steroid and thyroid hormones directly bind to nuclear receptors, which induce expression of specific genes. Recent global analyses of gene transcripts revealed that specific transcription factors (TFs) and their networking systems physiologically correspond to the onset of human diseases, including cancer. In other words, expression of specific genes might have relevance to pathogenesis of diseases. Given that OKSM (Yamanaka) factors convert somatic cells into induced pluripotent stem (iPS) cells, alterations in transcriptional state could affect destiny of the cells. In this chapter, revisiting known TFs, we would argue if transcription controlling strategies could contribute for the novel therapies on

Transcription factors are divided into two groups. First, the general TFs (GTFs), including preinitiation complex components TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and THIIH, are the primary protein factors that are required for the initiation of transcription from the TATA box (or TATA element), then elongation is executed by RNA polymerase II (RNA pol II) [1]. The others are the site-specific TFs or the DNA

Molecular mechanisms of the initiation of transcription from TATA box have been well known as the most essential nuclear events in mammalian cells. However, about 70% of mammalian gene promoters have no TATA or TATA-like elements, and they are referred to as TATA-less promoters [2]. In yeast cells, most of genes are regulated by the same general TF-dependent system independent of TATA or TATA-like sequences [3]. TATA-containing and TATA-less promoters
