Chapter 17 Lecture. Concepts of Genetics. Tenth Edition. Regulation of Gene Expression in Eukaryotes

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1 Chapter 17 Lecture Concepts of Genetics Tenth Edition Regulation of Gene Expression in Eukaryotes

2 Chapter Contents 17.1 Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNA to Protein Product 17.2 Programmed DNA Rearrangements Regulate Expression of a Small Number of Genes 17.3 Eukaryotic Gene Expression Is Influenced by Chromatin Modifications 17.4 Eukaryotic Transcription Initiation Is Regulated at Specific Cis-Acting Sites 2

3 Chapter Contents 17.5 Eukaryotic Transcription Initiation Is Regulated by Transcription Factors That Bind to Cis-Acting Sites 17.6 Activators and Repressors Interact with General Transcription Factors at the Promoter 17.7 Gene Regulation in a Model Organism: Transcription of the GAL genes of Yeast 3

4 Chapter Contents 17.8 Posttranscriptional Gene Regulation Occurs at All the Steps from RNA Processing to Protein Modification 17.9 RNA Silencing Controls Gene Expression in Several Ways 4

5 17.1 Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNA to Protein Product 5

6 Section 17.1 Gene regulation in eukaryotes is more complex than it is in prokaryotes because of the larger amount of DNA that is associated with histones and other proteins most genes of mrnas must be spliced, capped, and polyadenylated prior to transport from nucleus chromosomes with many genes are enclosed in a double membrane nucleus of movement of RNAs into cytoplasm after transcription of RNA stability of modulation of mrna translation as well as protein processing, modification, and degradation 6

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8 17.2 Programmed DNA Rearrangements Regulate Expression of a Small Number of Genes 8

9 Section 17.2 Genomic DNA in most organisms is stable; however, some gene regulation by DNA rearrangement exists DNA (gene) amplification DNA rearrangements during developmental regulation Creation of new gene from gene fragments Switch in expression of genes due to recombination Loss of DNA sequences in somatic cells 9

10 Section 17.2 Antigen recognition allows the immune system to bind to foreign substances (antigens) Humoral immunity involves production of immunoglobins (antibodies) that directly bind to antigens Synthesized by B cells that are made up of four variable regions allowing recognition of a specific antigen Each B cell synthesizes only one type of immunoglobulin DNA rearrangements can contribute to antibody diversity 10

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12 Section 17.2 The human k light-chain gene is assembled during B-cell development from multiple regions along chromosome 2 DNA regions organized into L (leader) and V (variable) regions Antibody diversity occurs in part from the random recombination of one of different functional LV regions with any of five different J regions 12

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14 Section 17.2 Two other mechanisms further increase antibody diversity Imprecise recombination between any particular pair of LV and J regions shows considerable variation High hypermutation (random somatic mutation) introduces more variation into the LVJ region s sequence 14

15 17.3 Eukaryotic Gene Expression Is Influenced by Chromatin Modifications 15

16 Section 17.3 Chromosomes occupy a discrete territory in the nucleus and stay separate from other chromosomes Transcription and translation spatially distinct Eukaryotic DNA combined with histone and nonhistone proteins to form chromatin Chromatin structure inhibits transcription, replication, and DNA repair 16

17 Section 17.3 During interphase, each chromosome occupies a discrete area called chromosome territory Channels between chromosomes are called interchromosomal domains Chromosome structure is continuously rearranged so that transcriptionally active genes are cycled to the edges of chromosome territories Transcription factories are nuclear sites that contain most of the active RNA polymerase and transcription regulatory molecules 17

18 Section 17.3 Chromatin remodeling is an important step in gene regulation and involves changes to either the nucleosome or DNA Most histones contain normal histones H2A and H3 Variant histones (H2A.Z and H3.3) can facilitate gene transcription Histone acetylation of the nucleosome is catalyzed by histone acetyltransferase enzymes (HATs) and is associated with increased transcription Histones can also be modified by phosphorylation and methylation 18

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20 Section 17.3 Chromatin remodeling involves repositioning or removal of nucleosomes on DNA Repositioned nucleosomes make regions of the chromosome accessible to transcription regulatory proteins Transcription activators RNA polymerase II The SWI/SNF is one of the best-studied remodeling complexes 20

21 Section 17.3 DNA methylation is associated with decreased gene expression Methylation occurs most often on the cytosine of CG doubled in DNA Methylation can repress transcription by binding to transcription factors of DNA 21

22 17.4 Eukaryotic Transcription Initiation Is Regulated at Specific Cis-Acting Sites 22

23 Section 17.4 Transcription regulation requires binding of many regulatory factors to specific DNA sequences (cis-acting sequences) Cis-acting sequence is located on the same chromosome as the gene that it regulates Promoters, Enhancers, Silencers 23

24 Section 17.4 Promoters are nucleotide sequences that serve as recognition sites for the transcription machinery Critical for initiation of transcription Located adjacent to genes regulated Great diversity exits in promoters in terms of structure and function Focused promoters: Specific transcription start site Dispersed promoters: Several start sites 24

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26 Section 17.4 Promoters are made up of one or more core elements that bind to specific initiation proteins Initiator (Inr), TATA box, TFIIB recognition element (BRE), downstream promoter element (DPE), and motif ten element (MTE) 26

27 Many promoters contain proximal promoter elements located upstream of the TATA and BRE motifs, enhancing levels of basal transcription CAAT and GC boxes 27

28 Section 17.4 Enhancers (cis-acting) are modular and contain several short DNA sequences increasing transcription rates Located on either side of gene, some distance from gene, or even within the gene Silencers are cis-acting elements that repress the level of transcription initiation 28