Regulation of Gene Expression CHAPTER 18

Bacterial Genome & Replication Section 18.1 : Bacteria can respond to environmental change by regulating gene transcription Bacterial Genome & Replication double-stranded, circular DNA located in the nucleoid region many bacteria also have plasmids – smaller circles of DNA with a few genes reproduce by binary fission therefore, most bacteria in a colony are genetically identical genetic diversity can arise as a result of mutation especially when reproductive rates are high (short generation spans)

Metabolic Control in Bacteria adjust the activity of enzymes already present via chemical cues (ex) feedback inhibition adjust the amount of enzyme being made by regulating gene expression basic mechanism is described in the operon model

Operons operator gene A gene B gene C gene D promoter made up of an operator, promoter, & a set of functionally related genes operator = segment of DNA that acts like an on/off switch for transcription; positioned w/in promoter or between promoter & genes promoter = site where RNA polymerase binds to DNA & begins transcription set of genes = transcription unit

Example: trp operon

lac operon repressor protein requires a small molecule called an inducer to make the repressor inactive (the repressor ‘unblocks’ the path)

Section 18.2 : Gene expression can be regulated at any stage

Regulation at Structural Levels of DNA a single linear DNA double helix averages about 4 cm in length DNA associates with proteins that condense it so it will fit in the nucleus DNA-protein complex = chromatin chromatin looks like “beads on a string” when unfolded “beads” = nucleosomes made up of histones (proteins) “string” = DNA

Structural Levels of DNA

chromatin fiber (30 nm) chromatin fiber (300 nm) chromosome created by interactions between adjacent nucleosomes and the linker DNA chromatin fiber (300 nm) created when the 30 nm chromatin fiber forms loops called looped domains attached to a protein scaffold made of nonhistones chromosome forms when the 300 nm chromatin fiber folds on itself

Regulation of Chromatin Structure compactness of chromatin helps regulate gene expression heterochromatin – highly compact so it is inaccessible to transcription enzymes euchromatin – less compact allowing transcription enzymes access to DNA chemical modifications that can alter chromatin compactness: histone acetylation (-COCH3) neutralizes the histones so they no longer bind to neighboring nucleosomes causing chromatin to have a looser structure

DNA Methylation addition of methyl groups to DNA bases (usually cytosine) inactivates DNA methylation patterns can be passed on after DNA replication, methylation enzymes correctly methylate the daughter strand accounts for genomic imprinting in mammals – expression of either the maternal or paternal allele of certain genes during development (NOTE: inheritance of chromatin modifications that do not involve a change in the DNA sequence is called epigenetic inheritance)

Regulation at Transcription Regulation at level of transcription results in differential gene expression Most common way that gene expression is regulated

Regulation of Transcription Initiation general transcription factors – proteins that form a transcription initiation complex on the promoter sequence (ex: TATA box) allowing RNA polymerase to begin transcription control elements – segments of noncoding DNA that help regulate transcription by binding certain proteins proximal control elements distal control elements (enhancers) - interact with specific transcription factors: activators –stimulate transcription by binding to enhancers repressors - inhibit transcription by binding directly to enhancers or by blocking activator binding to enhancers or other transcription machinery

activators bind to enhancer with 3-binding sites a DNA-bending protein brings the bound activators closer to the promoter activators bind to general transcription factors & mediator proteins, helping them to form a functional transcription initiation complex activators can also promote histone acetylation & repressors can promote histone deacetylation

Enhancer Promoter Albumin gene Control elements Crystallin gene Fig. 18-10 Enhancer Promoter Albumin gene Control elements Crystallin gene LIVER CELL NUCLEUS LENS CELL NUCLEUS Available activators Available activators Albumin gene not expressed Figure 18.10 Cell type–specific transcription Albumin gene expressed Crystallin gene not expressed Crystallin gene expressed (a) Liver cell (b) Lens cell

Regulation of RNA splicing In alternative RNA splicing, different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns

Exons DNA Troponin T gene Primary RNA transcript RNA splicing mRNA or Fig. 18-11 Exons DNA Troponin T gene Primary RNA transcript Figure 18.11 Alternative RNA splicing of the troponin T gene RNA splicing mRNA or

Regulation of Protein Lifespan After translation, various types of protein processing, including cleavage and the addition of chemical groups, are subject to control Proteasomes are giant protein complexes that bind protein molecules and degrade them

Proteasome and ubiquitin to be recycled Ubiquitin Proteasome Fig. 18-12 Proteasome and ubiquitin to be recycled Ubiquitin Proteasome Protein to be degraded Ubiquitinated protein Protein fragments (peptides) Protein entering a proteasome Figure 18.12 Degradation of a protein by a proteasome

Gene Regulation 7 6 protein processing & degradation 1 & 2. transcription - DNA packing - transcription factors 3 & 4. post-transcription - mRNA processing - splicing - 5’ cap & poly-A tail - breakdown by siRNA 5. translation - block start of translation 6 & 7. post-translation - protein processing - protein degradation 5 4 initiation of translation mRNA processing 2 1 initiation of transcription mRNA protection mRNA splicing 4 3

Section 18.4 : A program of differential gene expression leads to different cell types in a multicellular organism

Embryonic Development Zygote transforms as a result of 3 processes: cell division Number of cells increases through mitosis cell differentiation process by which cells become specialized in structure & function morphogenesis Organization of cells into tissues and organs *Cell differentiation arises primarily from differences in gene expression not from differences in the cells’ genomes* - Differentiation and morphogenesis are controlled by both cytoplasmic determinants and cell to cell signals

Cytoplasmic Determinants maternal substances in the egg that influence the course of early development distributed unevenly to new cells produced by mitotic division of the zygote the set of cytoplasmic determinants a cell receives helps regulate gene expression

Cell to Cell Signals communication between cells can induce differentiation Process is called induction

Determination the events that lead to the observable differentiation of a cell at the end of this process, an embryonic cell is irreversibly committed to its final fate (determined) marked by the expression of genes for tissue specific proteins, which act as transcription factors for genes that help define cell type

Pattern Formation development of a spatial organization in which the tissues and organs of an organism are all in their characteristic places begins in early embryo when the major axes of the organism are established molecular cues (positional information) that control pattern formation are provided by cytoplasmic determinants & inductive signals

Identity of Body Parts controlled by homeotic genes turned on by segment-polarity gene products specify the types of appendages and other structures that each segment will form (why are homeotic genes found in clusters?)

Example of a homeotic gene : PAX-6

Section 18.5 : Cancer results from genetic changes that affect cell cycle control The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development Cancer can be caused by mutations to genes that regulate cell growth and division Tumor viruses can cause cancer in animals including humans Oncogenes are cancer-causing genes Proto-oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division