1 Control of Gene Expression
2 What is Gene Expression? Gene expression is the process by which informa9on from a gene is used in the synthesis of a func9onal gene product.
3 What is Gene Expression? Figure 7-1 Molecular Biology of the Cell ( Garland Science 2008)
4 The difference The differences between a neuron, a lymphocyte, a pancreas cell, and a red blood cell depend on. precise control of gene expression. Or Cell differen9a9on is achieved by changes in gene expression.
5 The different cell types of a mul9cellular organism contain the same DNA
6 Figure 7-2a Molecular Biology of the Cell ( Garland Science 2008)
7 Figure 7-2b Molecular Biology of the Cell ( Garland Science 2008)
8 Figure 7-2c Molecular Biology of the Cell ( Garland Science 2008)
9 Different Cell Types Produce Different Sets of Proteins 1- Many processes are common to all cells (have many proteins in common). The housekeeping proteins (Structural proteins of the chromosomes, RNA polymerases, DNA repair enzymes, ribosomal proteins, )
10 2- Some proteins are abundant in the specialized cells (hemoglobin is only in red blood cells). 3- At any one 9me, a typical human cell expresses 30 60% of its approximately 25,000 genes. The level of expression of almost every ac9ve gene varies from one cell type to another.
11 Figure 7-3 Molecular Biology of the Cell ( Garland Science 2008)
12 4- Proteins can be covalently modified ayer they are synthesized.
13 Figure 7-4 Molecular Biology of the Cell ( Garland Science 2008)
14 A cell can change the expression of its genes in response to external signals Liver cell exposed to a glucocor9coid>>increase the produc9on of glucose from aa and other small molecules>>tyrosine aminotransferase. Fat cells> tyrosine aminotransferase is reduced.
15 GE can be regulated at many of the steps in the pathway from DNA to RNA to protein Figure 7-5 Molecular Biology of the Cell ( Garland Science 2008)
16 Gene Regulatory Proteins Gene regulatory proteins, the proteins specialized for switching genes on and off
17 Regulatory DNA Sequences Promoter region a^racts RNA polymerase>>>rna copy of the gene Promoter region has ini9a9on site where the transcrip9on begins. RNA polymerase binding sites of promoter. In addi9on to promoter nearly all genes have regulatory DNA sequences that used to the gene on or off
18 So??? Regulatory DNA sequences do not work themselves. So??? To have any effect these sequences must be recognized by the proteins called Gene regulatory proteins.
19 How these bind to DNA? In most cases protein binds to the major grove of the DNA helix. Figure 7-6 Molecular Biology of the Cell ( Garland Science 2008) Hydrogen bonds, Ionic bonds Hydrophobic interac9ons with the edges of the bases usually without disrup9ng the hydrogen bonds that hold the base pairs together
20 Figure 7-7 Molecular Biology of the Cell ( Garland Science 2008)
21 Table 7-1 Molecular Biology of the Cell ( Garland Science 2008)
22 Figure 7-9 Molecular Biology of the Cell ( Garland Science 2008)
23 DNA binding mo9fs
24 Helix- turn- helix Figure 7-10 Molecular Biology of the Cell ( Garland Science 2008)
25 Figure 7-11 Molecular Biology of the Cell ( Garland Science 2008)
26 Homeodomain Protein (Helix- turn- helix) Figure 7-13 Molecular Biology of the Cell ( Garland Science 2008)
27 Figure 7-14 Molecular Biology of the Cell ( Garland Science 2008) Zinc Finger
28 Figure 7-15 Molecular Biology of the Cell ( Garland Science 2008) Zinc Finger
29 Figure 7-19 Molecular Biology of the Cell ( Garland Science 2008) Leucine Zipper
30 Repressors Turn Genes Off, Ac9vators Turn Them On Figure 7-34 Molecular Biology of the Cell ( Garland Science 2008)
31 Figure 7-35 Molecular Biology of the Cell ( Garland Science 2008)
32 Figure 7-36 Molecular Biology of the Cell ( Garland Science 2008)
33 Human Genetics Concepts and Applications Tenth Edition RICKI LEWIS 11 Gene Expression and Epigenetics PowerPoint Lecture Outlines Prepared by Johnny El-Rady, University of South Florida Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
34 Gene Expression Through Time and Tissue Changes in gene expression may occur over time and in different cell types This may occur at the molecular, tissue, or organ/gland level Epigenetic changes - Changes to the chemical groups that associate with DNA that are transmitted to daughter cells after cell division
35 Hemoglobin Adult hemoglobin has four globular polypeptide chains - Two alpha (α) chains = 141 amino acids - Encoded on chromosome 11 - Two beta (β) chains = 146 amino acids - Encoded on chromosome 16
36 Hemoglobin Each globin surrounds an iron-containing heme group Figure 11.1
37 Globin Chain Switching Subunits change in response to oxygen levels Subunit makeup varies over lifetime - Embryo = Two epsilon (ε) + two zeta (ζ) - Fetus = Two gamma (γ) + two alpha (α) - Adult = Two beta (β) + two alpha (α) - The adult type is about 99% of hemoglobins by four years of age
38 Globin Chain Switching Figure 11.2
39 Changing Gene Expression in Blood Plasma Blood plasma contains about 40,000 different types of proteins Changing conditions cause a change in the protein profile of the plasma Stem cell biology is shedding light on how genes are turned on and off
40 Pancreas The pancreas is a dual gland - Exocrine part releases digestive enzymes into ducts - Endocrine part secretes polypeptide hormones directly into the bloodstream
41 Pancreas Differential gene expression produces either endocrine or exocrine cells If transcription factor pdx-1 is activated, some progenitor cells follow the exocrine pathway Other progenitor cells respond to different signals and yield daughter cells that follow the endocrine pathway
42 Figure 11.3 Figure 11.4!
43 Proteomics Proteomics tracks all proteins made in a cell, tissue, gland, organ or entire body Proteins can be charted based on the relative abundance of each class at different stages of development There are fourteen categories of proteins - Including the immunoglobulins, which are activated after birth
44 Figure 11.4 Figure 11.5!
45 Control of Gene Expression A protein-encoding gene contains some controls over its own expression level - Promoter sequence (mutations) - Extra copies of gene Much of the control of gene expression occurs in two general processes 1) Chromatin remodeling = On/off switch 2) micrornas = Dimmer switch 3) Regulatory Proteins
46 Chromatin Remodeling Histones play major role in gene expression - Expose DNA when and where it is to be transcribed and shield it when it is to be silenced The three major types of small molecules that bind to histones are: - Acetyl group - Methyl groups - Phosphate groups
47 Chromatin Remodeling Figure 11.5
48 Acetyl binding can subtly shift histone interactions in a way that eases transcription Figure 11.6
49 MicroRNAs MicroRNAs belong to a class of molecules called noncoding RNAs They are bases long The human genome has about 1,000 distinct micrornas that regulate at least 1/3 rd of the protein-encoding genes When a microrna binds to a target mrna, it prevents translation
50 Figure 11.7
51 MicroRNAs Cancer provides a practical application of micrornas because certain micrornas are more or less abundant in cancer cells than in healthy ones A related technology is called RNA interference (RNAi) - Small synthetic, double-stranded RNA molecules are introduced into selected cells to block gene expression
52 Maximizing Genetic Information The human genome contains about 20,325 genes - However, these encode about 100,000 mrnas, which in turn specify more than a million proteins Several events account for the fact that proteins outnumber genes
53 Maximizing Gene9c Informa9on Figure 11.8 Figure 11.11!
54 Maximizing Genetic Information The genes in pieces pattern of exons and introns and alternate splicing help to greatly expand the gene number Figure 11.9
55 Maximizing Genetic Information An intron in one gene s template strand may encode a protein on the coding strand Information is also maximized when a protein undergoes post-translational modifications - Addition of sugars and lipids to create glycoproteins and lipoproteins
56 Maximizing Genetic Information Another way that one gene can encode more than one protein is if the protein is cut to yield two products This happens in dentinogenesis imperfecta - Caused by a deficiency in the two proteins DPP and DSP - Both are cut from the same DSPP protein
57 Den9nogenesis Imperfecta Caused by deficiency in proteins DPP and DSP" Both are cut from same Figure larger protein"
58 DPP and DSP Figure Figure 11.13b!
59 Most of the Human Genome Does Not Encode Protein Only 1.5% of human DNA encodes protein Rest of genome includes: - Viral DNA - Noncoding RNAs - Introns - Promoters and other control sequences - Repeated sequences
60 Noncoding RNAs Nearly all of the human genome can be transcribed, and much of it is in the form of noncoding RNAs (ncrnas) This includes rrnas and trnas However, there are hundreds of thousands of other ncrnas - These are transcribed from pseudogenes - But are not translated into protein