GENE REGULATION IN EUKARYOTE definition of gene regulation gene regulation in eukaryotes

VIETNAM GENERAL CONFEDERATION OF LABOUR TON DUC THANG UNIVERSITY FACULTY OF APPLIED SCIENCE GENETICS REPORT GENE REGULATION IN EUKARYOTE Instructing lecturer: ph.D Trần Thị Dung Group: 04 Phạm Quí Tâm – 620H0234 Lương Thị Quỳnh Mai – 620H0273 Ho Chi Minh City, 2021 i ACKNOWLEGDEMENT First, I would like to thank Ton Duc Thang University for giving me the opportunity to access learning Biosafety In particular, I would like to express my deep thanks to my lecturer – Tran Thi Dung for imparting valuable, influential and highly applicable lessons From what you conveyed, I gradually expand my knowledge, comprehend the small world that the naked eye could not see, understand how we can be different from others and the mechanism of gene expression and so on Perhaps knowledge is endless and each person's acquisition has certain limitations For over the year, our country has also been heavily affected by the Covid-19 pandemic leading to our knowledge disruption Therefore, in the process of completing the report, it is inevitable to avoid the shortcomings or mistakes I look forward to receiving comments from you to gain more experience for later reports and essays I would like to sincerely thank and wish you and other teachers have excellent health to overcome this pandemic together ii TABLE OF CONTENTS ACKNOWLEGDEMENT i TABLE OF CONTENTS ii LIST OF ABBREVIATIONS iii LIST OF TABLES iii LIST OF PICTURES iv INTRODUCTION v CHAPTER 1: DEFINITION OF GENE REGULATION 1.1 Definition of gene regulation 1.2 Funtion 1.3 Difference between prokaryote eukaryote regulation 1.4 The fundermental mechanism of gene regulation CHAPTER 2: GENE REGULATION IN EUKARYOTES 2.1 Chromatin accessibility 2.2 Transcription 2.3 Regulation of RNA processing 2.4 RNA stability 10 2.5 Translation 11 2.6 Protein activity 12 REFERENCES 14 RESPONSIBILITY 19 iii LIST OF ABBREVIATIONS DNA DeoxyriboNucleic Acid eIF-2 Eukaryotic initiation factor - mRNA Messenger RNA RNA RiboNucleic acid iii LIST OF TABLES Table 1.1 Difference between prokaryote and eukaryote gene regulation iv LIST OF PICTURES Chapter Picture 1.1 How liver cell removes toxic subtances Picture 1.2 llustration how gene can be expressed Chapter Picture 2.1 Chromatine accessibility and the regulatory epigenome Picture 2.2 Stages of transcription 10 Picture 2.3 Alternative splicing process 11 Picture 2.4 Role of miRNA biogenesis in gene expression 12 Picture 2.5 what will happen if eIF-2 is phosphorylated? 13 Picture 2.6 Protein structure 14 v INTRODUCTION As we know three processes set up for cell survival, namely: replication, version coding and translation coding However, cells cannot exist independently with their surroundings Thus, an important question arises: how does cell adapt its activity to changes in the external environment in order to survive the appropriate condition? The purpose of our group through this report is giving the detailed information about gene regulation and expression This report consists of two chapters: Chapter 1: Definition of gene regulation Chapter 2: Gene regulation in Eukaryotes CHAPTER 1: DEFINITION OF GENE REGULATION 1.1 Definition of gene regulation Gene regulation is the informal term used to describe any mechanism used by a cell to increase or decrease the production of specific gene products (protein or RNA) [1] These include structural and chemical changes to the genetic material, binding of proteins to specific DNA elements to regulate transcription, or mechanisms that modulate translation of mRNA [2] For example, one of the jobs of the liver is to remove toxic substances like alcohol from the bloodstream To this, liver cells express genes encoding subunits (pieces) of an enzyme called alcohol dehydrogenase This enzyme breaks alcohol down into a non-toxic molecule The neurons in a person's brain don’t remove toxins from the body, so they keep these genes unexpressed, or “turned off.” [3] Picture 1.1 How liver cell removes toxic subtances 1.2 Funtion To maintain homeostasis and development of the organism, organisms have different regulatory mechanisms Regulatory patterns are derived from the expression of genes [4] Thanks to gene regulation, each cell type in your body has a different set of active genes – despite the fact that almost all the cells of your body contain the exact same DNA These different patterns of gene expression cause your various cell types to have different sets of proteins, making each cell type uniquely specialized to its job [3] Gene regulation ensures that the appropriate genes are expressed at the proper times Gene regulation can also help an organism respond to its environment 1.3 Difference between prokaryote eukaryote regulation Gene regulation in Eukaryote is more complex than in Prokaryote Table 1.1 Difference between prokaryote and eukaryote gene regulation Eukaryotes - Transcription occurs inside the nucleus [5] Prokaryote The entire prokaryotic gene - Translation occurs in the cytoplasm [5] expression occurs in the Occurs at various steps of gene expression, cytoplasm [5] Mainly occurs at the facilitated by the compartmentalization of transcriptional level [5] the gene expression [5] Transcription and Translation are Transcription and Translation temporally segregated [5] Splicing of introns and joining of exons is occurs simultaneously [5] don't contain introns [6] needed [6] 80S ribosomes 70S ribosomes 1.4 The fundermental mechanism of gene regulation In chromatin, or the complex of DNA and histone proteins found within the cellular nucleus The histones are among the most evolutionarily conserved proteins known; they are vital for the well-being of eukaryotes and brook little change When a specific gene is tightly bound with histone, that gene is "off." But how, then, eukaryotic genes manage to escape this silencing? This code includes modifications of the histones positively charged amino acids to create some domains in which DNA is more open and others in which it is very tightly bound up DNA methylation is one mechanism that appears to be coordinated with histone modifications, particularly those that lead to silencing of gene expression On the other hand, when the tails of histone molecules are acetylated at specific locations, these molecules have less interaction with DNA, thereby leaving it more open [7] Picture 1.2 Illustration how gene can be expressed CHAPTER 2: GENE REGULATION IN EUKARYOTES The regulation of gene expression in eukaryotes must go through more complex levels of regulation than in prokaryotes and go through several stages such as: chromosome uncoiling, transcription, post-transcriptional modification, mRNA leaving the nucleus to the cytoplasm, translation and post-translational transformation [4] 2.1 Chromatin accessibility The structure of chromatin (DNA and its organizing proteins) can be regulated More open or “relaxed” chromatin makes a gene more available for transcription [3] Picture 2.1 Chromatine accessibility and the regulatory epigenome 2.2 Transcription Transcription is a key regulatory point for many genes Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA [3] This type of regulation is common in metabolic regulation, as well as in cellular differentiation processes [4] - The effect of cis sequences (adjacent, adjacent) located on the same DNA strand as enhancer (enhancer region) increases transcription [4] 10 - Regulated by trans factors (spaced, remote) because the factors are not on the same DNA strand [4] - Select the appropriate promoter - Weakness or deterioration 2.3 Picture 2.2 Stages of transcription Regulation of RNA processing When a eukaryotic gene is transcribed in the nucleus, the primary transcript (freshly made RNA molecule) isn't yet considered a messenger RNA - it's a pre-mRNA The pre-mRNA has to go through some modifications to become a mature mRNA molecule that can leave the nucleus and be translated These include splicing, capping, and addition of a poly-A tail, all of which can potentially be regulated – sped up, slowed down, or altered to result in a different product [8] Most pre-mRNA molecules have sections that are removed from the molecule, called introns, and sections that are linked or together to make the final mRNA, called exons This process is called splicing [8] 11 In the process of alternative splicing, different portions of an mRNA can be selected for use as exons Picture 2.3 Alternative splicing process Alternative splicing is not a random process Instead, it's typically controlled by regulatory proteins The proteins bind to specific sites on the pre-mRNA and "tell" the splicing factors which exons should be used Different cell types may express different regulatory proteins, so different exon combinations can be used in each cell type, leading to the production of different proteins [8] 2.4 RNA stability Once an mRNA has left the nucleus, it may or may not be translated many times to make proteins Two key determinants of how much protein is made from an mRNA are its "lifespan" (how long it floats around in the cytosol) and how readily the translation machinery, such as the ribosome, can attach to it [8] A recently discovered class of regulators, called small regulatory RNAs, can control mRNA lifespan and translation [8] MicroRNAs (miRNAs) were among the first small regulatory RNAs to be discovered A miRNA is first transcribed as a long RNA molecule, which forms base pairs with itself and folds over to make a hairpin [8] 12 Picture 2.4 Role of miRNA biogenesis in gene expression 2.5 Translation ln order for translation to begin, the ribosome, an RNA-and-protein complex that houses translation, must assemble on the mRNA This process involves many “helper” proteins, which make sure the ribosome is correctly positioned Translation can be regulated globally (for every mRNA in the cell) through changes in the availability or activity of the “helper” proteins [8] In order for translation to begin, a protein called eukaryotic initiation factor-2 (eIF2) must bind to a part of the ribosome called the small subunit Binding of eIF-2 is controlled by phosphorylation, or addition of a phosphate group to the protein 13 When eIF-2 is phosphorylated, it's turned "off"—it undergoes a shape change and can no longer play its role in initiation, so translation cannot begin When eIF-2 is not phosphorylated, in contrast, it's "on" and can carry out its role in initiation, allowing translation to proceed [8] Picture 2.5 What will happen if eIF-2 is phosphorylated? 2.6 Protein activity Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups These modifications can be regulated and may affect the activity or behavior of the protein [3] After the polypeptide chain is synthesized, proteins often undergo secondary transformations before they become active (functional) Proteins can be subjected to stereogenic modifications such that the association of enzymes with specific products can alter their spatial structure leading to loss of activity [4] One of the most common post-translational modifications is phosphorylation, in which a phosphate group is attached to a protein The effect of phosphorylation varies from protein to protein: some are activated by phosphorylation, while others 14 are deactivated, and others yet simply change their behavior (interacting with a different partner or going to a different part of the cell) [8] Picture 2.6 Protein structure 15 REFERENCES Internet: [1] Gene Regulation: Definition & Overview, (Retrieved: 01:31 PM, 19/02/2022) From: https://study.com/academy/lesson/gene-regulation-definition-lessonquiz.html [2] Gene Regulation, (Retrieved: 02:31 PM, 19/02/2022) From: https://www.nature.com/subjects/gene-regulation#:~:text=Gene%20 regulation%20refers%20to%20the,that%20modulate%20translation%20of %20mRNA [3] Overview: Eukaryotic gene regulation, (Retrieved: 05:51 PM, 19/02/2022) From: https://www.khanacademy.org/science/ap-biology/gene-expressionand-regulation/regulation-of-gene-expression-and-cellspecialization/a/overview-of-eukaryotic-gene-regulation [4] Giáo trình Sinh học phân tử - Nguyễn Hồng Lộc, Điều hòa biểu gen (Retrieved: 06 PM 19/02/2022) From: https://www.sinhhocphantu.org/2018/06/ieu-hoa-bieu-hien-gen.html [5] Lakna, What is the Difference Between Prokaryotic and Eukaryotic Gene Expression, (2018, October 28) (Retrieved February 19, 2022) From https://pediaa.com/what-is-the-difference-between-prokaryotic-andeukaryotic-gene-expression/ [6] Kate M, How does gene regulation differ in prokaryotes and eukaryotes? (Sep 17, 2016), (Retrieved: 06:11 PM 19/02/2022) From: https://socratic.org/questions/how-does-gene-regulation-differ-inprokaryotes-and-eukaryotes 16 [7] Hoopes, L (2008), Introduction to the gene expression and regulation, Gene Expression and Regulation (Retrieved: 08:55 PM 19/02/2022) From: https://www.nature.com/scitable/topic/gene-expression-and-regulation15/ [8] Regulation after transcription, (Retrieved: 01:27 PM, 20/02/2022) From: https://www.khanacademy.org/science/biology/gene-regulation/generegulation-in-eukaryotes/a/regulation-after-transcription 17 RESPONSIBILITY Productivity Attitude Productivity Attitude Summary Productivity Attitude ... Chapter 1: Definition of gene regulation Chapter 2: Gene regulation in Eukaryotes CHAPTER 1: DEFINITION OF GENE REGULATION 1.1 Definition of gene regulation Gene regulation is the informal term... less interaction with DNA, thereby leaving it more open [7] Picture 1.2 Illustration how gene can be expressed CHAPTER 2: GENE REGULATION IN EUKARYOTES The regulation of gene expression in eukaryotes. .. prokaryote eukaryote regulation Gene regulation in Eukaryote is more complex than in Prokaryote Table 1.1 Difference between prokaryote and eukaryote gene regulation Eukaryotes - Transcription occurs inside