Regulation of Gene Expression in...
Transcript of Regulation of Gene Expression in...
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Chapter 17 Lecture
Concepts of Genetics Tenth Edition
Regulation of Gene Expression in Eukaryotes
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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
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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
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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
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17.1 Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from
DNA to Protein Product
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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
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17.2 Programmed DNA Rearrangements Regulate Expression of a Small Number
of Genes
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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
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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
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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 35–50 different functional LV regions with any of five different J regions
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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
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17.3 Eukaryotic Gene Expression Is Influenced by Chromatin Modifications
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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 non-histone proteins to form chromatin – Chromatin structure inhibits transcription, replication,
and DNA repair
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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
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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
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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
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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
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17.4 Eukaryotic Transcription Initiation Is Regulated at Specific Cis-Acting Sites
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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
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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
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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)
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• Many promoters contain proximal promoter elements located upstream of the TATA and BRE motifs, enhancing levels of basal transcription – CAAT and GC boxes
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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
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