《基因组学》课程教学资源（PPT课件讲稿）Chapter 14 基因组活性的调控 Regulation of Genome Activity

Chapter 14 Regulation of Genome Activity 1. Transient Changes in Genome Activity 2. Permanent and semipermanent changes in Genome Activity 3. Regulation of Genome Activity During Development

Chapter 14 Regulation of Genome Activity 1. Transient Changes in Genome Activity 2. Permanent and Semipermanent Changes in Genome Activity 3. Regulation of Genome Activity During Development

Table 14.1 Examples of steps in the genome expression pathway at which regulation can be exerted Example of regulation Transcription Gene accessibility Locus control regions determine chromatin structure in areas that contain genes (Section 10.1.2) Histone modifications influence chromatin structure and determine which genes are accessible(Section 10.2.1) Nucleosome positioning controls access of RNA polymerase and transcription factors to the promoter region (Section 10. 2.2 DNA methylation silences regions of the genome( Section 10.3.1) Initiation of transcription Productive initiation is influenced by activators, repressors, and other control systems (Section 11.3) Synthesis of RNA Prokaryotes use antitermination and attenuation to control the amount and nature of individual transcripts(Section 12. 1. 2)

Table 14.1 Examples of steps in the genome expression pathway at which regulation can be exerted Step Example of regulation Eukaryotic mRNA Processing Capping Some animals use capping as a means of regulating protein synthesis during egg maturation adenylation Alternative polyadenylation sites control flowering in Arabidopsis Translation of bicoid mRNA in Drosophila eggs is activated after fertilization by extension of the poly (A)tail(Section 14.3.4) Alternative splice site selection controls sex determination in Drosophila(Section 12.2. 2) Chemical modification RNA editing of apolipoprotein-B mRNA results in liver-and intestine-specific versions of this protein(Section 12.2.5) mRNA degradation MicroRNAs control cell death, specification of neuron cell types, and control of fat storage in Caenorhabditis elegans, as well as many diverse processes in other eukaryotes (Section 12.2.6) Iron controls degradation of transferrin receptor mRNA(Section 13. 2.2)

Table 14. 1 Examples of steps in the genome expression pathway at which regulation can be exerted Step Example of regulation Protein synthesis and processing Initiation of translation Phosphorylation of elF-2 results in a general reduction in translation initiation in eukaryotes (seon1322) Ribosomal proteins in bacteria control their own synthesis by modulating ribosome attachment to their mRNAs(Section 13. 2.2) In some eukaryotes, iron controls ribosome scanning on ferritin mRNAs(Section 13. 2.2) Small RNAs in bacteria regulate the response to oxidative stress by modulating initiation of translation of various mRNAs(Section 13. 2.2) Protein synthesis Frameshifting enables two DNA polymerase lll subunits to be translated from the Escherichia coli dnax gene(Section 13.2.3 Cutting events Alternative cleavage pathways for polyproteins result in tissue-specific protein products (Section 13.3.2) Chemical modification Many proteins involved in signal transduction are activated by phosphorylation (Section 14. 1.2)

How the activity of the genome as a whole is requlated Differentiation not only in multicellular organisms Human has over 250 types of specialized cells

How the activity of the genome as a whole is regulated. • Differentiation not only in multicellular organisms. • Human has over 250 types of specialized cells

14.1 Transient Changes in Genome activity Most cells in multicellular organisms live in less variable environments but the maintenance of this environment requires coordination between the activities of different cells To exert an effect on genome activity, the nutrient, hormone, growth factor, or other extracellular compound that represents the external stimulus must influence events within the cell

14.1 Transient Changes in Genome Activity • Most cells in multicellular organisms live in less variable environments, but the maintenance of this environment requires coordination between the activities of different cells. • To exert an effect on genome activity, the nutrient, hormone, growth factor, or other extracellular compound that represents the external stimulus must influence events within the cell

Direct activation Indirect activation signaling compound signal transduction enters the cell via a cell surface receptor Surface receptor ODD

14.1.1 Signal transmission by import of the extracellular signaling compound Signaling compound directly influences a protein factor Signaling com- pound is an activator o→ Genome repressor of transcription ⑩D Signaling compound indirectly influences a protein factor

14.1.1 Signal transmission by import of the extracellular signaling compound

Lactoferrin is an extracellular signaling protein Which acts as a transcription activator not a common mechanism difficulty in designing a protein that combines the hydrophobic properties needed for effective transport across a membrane with the hydrophilic properties needed for migration through the aqueous cytoplasm to the protein's site of action in the nucleus or on a ribosome.想想大宝SOD蜜的护肤机理 Lactoferrin play a role in the body's defenses against microbial attack, by reducing free-iron levels in milk, thereby starving invading microbes of this essential cofactor Its dna binding was shown to be sequence specific and to stimulate transcription, confirming that lactoferrin is a true transcription activator

Lactoferrin is an extracellular signaling protein which acts as a transcription activator • not a common mechanism • difficulty in designing a protein that combines the hydrophobic properties needed for effective transport across a membrane with the hydrophilic properties needed for migration through the aqueous cytoplasm to the protein‘s site of action in the nucleus or on a ribosome. 想想大宝SOD蜜的护肤机理。 • Lactoferrin: play a role in the body's defenses against microbial attack, by reducing free-iron levels in milk, thereby starving invading microbes of this essential cofactor. • Its DNA binding was shown to be sequence specific and to stimulate transcription, confirming that lactoferrin is a true transcription activator

Some imported signaling compounds directly influence the activity of pre-existing protein factors Environmental concentration of copper Lactose Nutritional Toxic copper and zinc Cu CuCucu Steroid hormones Cu CuCucu Cu Cu Cu Cu Cu Cu Cu Estrogen receptor C Cu Cu Progesterone receptor N Active Mac1p Active Acelp Glucocorticoid receptor CTR1 CUPT N sC CTR3 CRS5 200 amino ac FRET SOD1 KEY a Variable region DNA-binding domain Synthesis of copper- Synthesis of copper Hormone-binding domain uptake proteins detoxification proteins

Some imported signaling compounds directly influence the activity of pre-existing protein factors Lactose copper and zinc Steroid hormones