Chapter 15 Controls over Genes

Control over Genes All organisms must regulate which genes are expressed at any given time In multicellular organisms regulation of gene expression is essential for cell specialization 2

Differential Gene Expression Almost all the cells in an organism are genetically identical Differences between cell types result from differential gene expression the expression of different genes by cells with the same genome Abnormalities in gene expression can lead to diseases, including cancer 3

Signal NUCLEUS Chromatin Figure 15.6a Signal NUCLEUS Chromatin Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Figure 15.6a Stages in gene expression that can be regulated in eukaryotic cells (part 1: nucleus) Intron RNA processing Tail mRNA in nucleus Cap Transport to cytoplasm CYTOPLASM 4

Protein processing, such as cleavage and chemical modification Figure 15.6b CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Protein processing, such as cleavage and chemical modification Active protein Degradation of protein Figure 15.6b Stages in gene expression that can be regulated in eukaryotic cells (part 2: cytoplasm) Transport to cellular destination Cellular function (such as enzymatic activity, structural support) 5

Gene Control which genes are expressed in a cell depends upon: • type of cell • internal chemical conditions • external signals • built-in control systems

Control Mechanisms negative control regulatory proteins slow down or curtail gene activity positive control regulatory proteins promote or enhance gene activities

Controls in Eukaryotic Cells Controls of eukaryotic gene expression

Mechanisms of Gene Control Chromatin Structure Transcriptional Control Post Transcriptional Control Translational Control Post Translational Control

Chromatin Structure Chromatin a complex of DNA and protein Chromosomes fit into the nucleus through an elaborate, multilevel system of packing Chromatin undergoes striking changes in the degree of packing during the course of the cell cycle packing used to keep genes turned off can’t transcribed if highly condensed histones regulate accessibility to DNA 10

Chromatin Structure euchromatin loosely bound DNA can be expressed acetyl group heterochromatin tightly bound DNA inactive methylated

Unacetylated histones Acetylated histones Nucleosome Histone tails Unacetylated histones Acetylated histones Figure 15.7 A simple model of the effect of histone acetylation 12

Epigenetic Inheritance inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence though chromatin modifications do not alter DNA sequence, they may be passed to future generations of cells epigenetic modifications can be reversed, unlike mutations in DNA sequence epigenetics 13

Transcriptional Control controlled by DNA binding proteins transcription factors promoters transposons activators have two domains one that binds DNA a second that activates transcription ehancers increases transcription rates

Distal control element Enhancer TATA box Promoter Activators Gene DNA Distal control element Enhancer TATA box Figure 15.10-1 A model for the action of enhancers and transcription activators (step 1) 15

Distal control element Enhancer TATA box Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA- bending protein Group of mediator proteins Figure 15.10-2 A model for the action of enhancers and transcription activators (step 2) 16

Distal control element Enhancer TATA box Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA- bending protein Group of mediator proteins RNA polymerase II Figure 15.10-3 A model for the action of enhancers and transcription activators (step 3) RNA polymerase II Transcription initiation complex RNA synthesis 17

Post Transcriptional Control involves mRNA processing splicing of exons together occur determines how fast mRNA leaves the nucleus specific zip code

Translational Control determined by 5’, 3’ length of poly A tail enzymes begin degradation of the poly-A tail any influence on 3’ end can lead to destruction of mRNA

Post Translational Control some proteins are not immediately active some proteins are short lived ex.) cyclin Controls cell cycle cell has proteasomes carry out task of destroying proteins

X Chromosome Inactivation

X Chromosome Inactivation A condensed X chromosome (Barr body) in the somatic cell nucleus of a human female

Most Genes Are Turned Off Cells of a multi-celled organism rarely use more than 5-10 percent of their genes at any given time The remaining genes are selectively expressed

Homeotic Genes Occur in all eukaryotes Master genes that control development of body parts Encode homeodomains (regulatory proteins) Homeobox sequence can bind to promoters and enhancers

Gene Control in Prokaryotes No nucleus separates DNA from ribosomes in cytoplasm When nutrient supply is high, transcription is fast Translation occurs even before mRNA transcripts are finished

Prokaryotic Versus Eukaryotic Gene Control

Negative control of the lactose operon High Lactose Negative control of the lactose operon

The Lactose Operon operator regulatory gene gene 1 gene 2 gene 3 transcription, translation promoter lactose operon repressor protein

Low Lactose Repressor binds to operator Binding blocks promoter Transcription is blocked

CAP Exerts Positive Control CAP is an activator protein Adheres to promoter only when in complex with cAMP Level of cAMP depends on level of glucose

Positive Control – High Glucose There is little cAMP CAP cannot be activated The promoter is not good at binding RNA polymerase The lactose-metabolizing genes are not transcribed very much

Positive Control – Low Glucose cAMP accumulates CAP-cAMP complex forms Complex binds to promoter RNA polymerase can now bind The lactose-metabolizing genes are transcribed rapidly

Hormones Signaling molecules Stimulate or inhibit activity in target cells Mechanism of action varies May bind to cell surface May enter cell and bind to regulatory proteins May bind with enhancers in DNA

Vertebrate Hormones Some have widespread effects Somatotropin (growth hormone) Others signal only certain cells at certain times Prolactin stimulates milk production