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Alberts • Johnson • Lewis • Morgan • Raff • Roberts • Walter Molecular Biology of the Cell Sixth Edition Chapter 7 Control of Gene Expression Su-May Yu Copyright © Garland Science 2015 The Different Cell Types of a Multicellular Organism Contain the Same DNA The Different Cell Types of a Multicellular Organism Contain the Same DNA The Different Cell Types of a Multicellular Organism Contain the Same DNA Different Cell Types Synthesize Different Sets of RNAs and Proteins Different Cell Types Synthesize Different Sets of RNAs and Proteins IEP, is the pH at which a particular molecule carries no net electrical charge - - + + Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein The Sequence of Nucleotides in the DNA Double Helix Can Be Read by Proteins Major protein recognition site Major protein recognition site Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences • TF recognizes specific sequences of DNA (typically 5-10 bp). • These DNA sequences are called cis-regulatory sequences/elements. • The interaction is highly specific and very strong. Transcription regulator or transcription factor (TF) Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Dimers have a more strong binding affinity to DNA. Major groove Major groove Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Help to position the recognition helix Major groove Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Major groove Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Major groove Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Major groove Major groove Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences TF may contain > 1 activation domain, but rarely > 1 DNA-binding domain. Dimerization of Transcription Regulators Increases Their Affinity and Specificity for DNA • • Cis-regulatory sequences are read as double-stranded DNA, but only one strand is shown in a logo. The same TF can be “reused” or becomes partner or other TFs. A homeodomain transcript factor in embryonic stem cells homo homo Regulation of Chromatin Structure • Genes within highly packed heterochromatin are usually not expressed • Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression © 2011 Pearson Education, Inc. Nucleosome Structure Promotes Cooperative Binding of Transcription Regulators The Tryptophan Repressor Switches Genes Off The Tryptophan Repressor Switches Genes Off Repressors Turn Genes Off and Activators Turn Them On An Activator and a Repressor Control the Lac Operon • Lactose is a disaccharide sugar composed of galactose and glucose that is found in milk. • The gene product of lacZ is β-galactosidase (activator) DNA Looping Can Occur During Bacterial Gene Regulation Organization of a Typical Eukaryotic Gene TATA box – for positioning RNA polmerase II to initiate transcription Enhancer (distal control elements) Proximal control elements Transcription start site Exon DNA Upstream Intron Exon Intron Downstream Poly-A signal Intron Exon Exon Cleaved 3′ end of primary RNA processing transcript Promoter Transcription Exon Primary RNA transcript 5′ (pre-mRNA) Poly-A signal Transcription sequence termination region Intron Exon Intron RNA Coding segment mRNA G P AAA ⋅⋅⋅ AAA P P 5′ Cap 5′ UTR Start Stop codon codon 3′ UTR Poly-A tail 3′ A Eukaryotic Gene Control Region Consists of a Promoter Plus Many cis-Regulatory Sequences Could be chromatin remodeling complex Multi-protein co-activator Figure 11-1 Overview of transcription control in multicellular eukaryotes. The Sequence of Nucleotides in the DNA Double Helix Can Be Read by Proteins Histone acetyltransferase Histone deacetylase Acetylation removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription. Eukaryotic Transcription Activators Direct the Modification of Local Chromatin Structure Transcription Activators Work Synergistically Eukaryotic Transcription Repressors Can Inhibit Transcription in Several Ways Eukaryotic Transcription Activators Direct the Modification of Local Chromatin Structure Chromatin is tightly condensed and in a transcriptionally silent form -CH3 Figure 7-50d Molecular Biology of the Cell (© Garland Science 2008) Transcription Regulators Are Brought Into Play by Extracellular Signals The Drosophila Eve Gene Is Regulated by Combinatorial Controls Figure 18.11 Enhancer Control elements Promoter Albumin gene Crystallin gene LENS CELL NUCLEUS LIVER CELL NUCLEUS Available activators Available activators Albumin gene not expressed Albumin gene expressed Crystallin gene not expressed (a) Liver cell Crystallin gene expressed (b) Lens cell Specialized Cells Must Rapidly Turn Sets of Genes On and Off GUS Signals in dead cells SUC2:GUS SUC2:GFP ABRC:GUS DR5:GUS Signals in live cells Green fluorescence proteins as reporters Promoter:GFP promoter activity Promoter:GFP-protein protein localization Temporally or specially regulated promoter Constitutive and strong promoter Complex Genetic Switches That Regulate Drosophila Development Are Built Up from Smaller Molecules Complex Genetic Switches That Regulate Drosophila Development Are Built Up from Smaller Molecules The Drosophila Eve Gene Is Regulated by Combinatorial Controls Combinatorial Gene Control Creates Many Different Cell Types Combinatorial Gene Control Creates Many Different Cell Types Combinatorial Gene Control Creates Many Different Cell Types Combinations of Master Transcription Regulators Specify Cell Types by Controlling the Expression of Many Genes Transcription Circuits Allow the Cell to Carry Out Logic Operations Transcription Circuits Allow the Cell to Carry Out Logic Operations The Sequence of Nucleotides in the DNA Double Helix Can Be Read by Proteins
