Key Concepts Changes in gene expression allow eukaryotic cells to respond to changes in the environment and cause distinct cell types to develop Eukaryotic DNA is packaged with proteins into structures that must be opened before transcription can occur In eukaryotes transcription is triggered by regulatory proteins that bind to the promoter and to sequences close to and far from the promoter 2011 Pearson Education Inc Key Concepts Once transcription is complete gene expression is controlled by 1 Alternative splicing which allows a single gene to code for several different products 2 Molecules that regulate the life span of mRNAs 3 Activation or inactivation of protein products Cancer can develop when mutations disable genes that regulate cell cycle control genes 2011 Pearson Education Inc Introduction The regulation of gene expression is more complex in eukaryotes than in prokaryotes Differential gene expression is responsible for creating different cell types arranging them into tissues and coordinating their activity to form the multicellular society we call an individual 2011 Pearson Education Inc Mechanisms of Gene Regulation An Overview Like prokaryotes eukaryotes can control gene expression at the levels of transcription translation and post translation Three additional levels of control are unique to eukaryotes 1 Chromatin remodeling 2 RNA processing 3 Regulation of mRNA life span or stability 2011 Pearson Education Inc 2011 Pearson Education Inc Chromatin Remodeling In eukaryotes DNA is wrapped around proteins to create a proteinDNA complex called chromatin RNA polymerase cannot access the DNA when it is supercoiled within the nucleus The DNA near the promoter must be released from tight interactions with proteins before transcription can begin this process is called chromatin remodeling 2011 Pearson Education Inc RNA Processing and Control of mRNA Stability Transcription results in a primary RNA transcript that must undergo RNA processing to produce a mature mRNA mRNA stability or the life span of the mRNA can also be used to control gene expression 2011 Pearson Education Inc What Is Chromatin s Basic Structure Chromatin has a regular structure with several layers of organization Chromatin contains nucleosomes repeating beadlike structures Nucleosomes consist of negatively charged DNA wrapped twice around eight positively charged histone proteins A histone protein called H1 functions to maintain the structure of each nucleosome Between each pair of nucleosomes there is a linker stretch of DNA 2011 Pearson Education Inc What Is Chromatin s Basic Structure H1 histones also may interact with each other and with histones in other nucleosomes to form a tightly packed structure called a 30nanometer fiber These 30 nanometer fibers in turn may form higher order structures Chromatin s elaborate structure not only allows the DNA to be packaged in the nucleus it also plays a key role in regulating gene expression 2011 Pearson Education Inc 2011 Pearson Education Inc Chromatin Structure Is Altered in Active Genes As in bacteria eukaryotic DNA has sites called promoters where RNA polymerase binds to initiate transcription Studies support the idea that chromatin must be relaxed or decondensed for RNA polymerase to bind to the promoter 2011 Pearson Education Inc Closed DNA Is Protected from DNase DNase is an enzyme that cuts DNA at random locations The enzyme cannot cut DNA when it is tightly complexed with histones 2011 Pearson Education Inc 2011 Pearson Education Inc Histone Mutants Studies of mutant brewer s yeast cells led biologists to hypothesize that the lack of histone proteins prevents the assembly of normal chromatin These data suggest that the default state of eukaryotic genes is to be turned off This is a mechanism of negative control A form of positive control must be at work to open up DNA at promoter regions for gene expression to occur 2011 Pearson Education Inc How Is Chromatin Altered Two major types of protein are involved in modifying chromatin structure 1 ATP dependent chromatin remodeling complexes reshape chromatin 2 Other enzymes catalyze the acetylation addition of acetyl groups and methylation addition of methyl groups of histones Acetylation of histones is usually associated with activation of genes Methylation can be correlated with either activation or inactivation 2011 Pearson Education Inc How Is Chromatin Altered One type of acetylation enzyme is called histone acetyl transferases HATs They add negatively charged acetyl groups to the positively charged lysine residues in histones This acetylation reduces the positive charge on the histones decondensing the chromatin and allowing gene expression Enzymes called histone deacetylases HDACs then remove the acetyl groups from histones This reverses the effects of acetylation and allows chromatin condensation 2011 Pearson Education Inc 2011 Pearson Education Inc Chromatin Modifications Can Be Inherited The pattern of chemical modifications on histones varies from one cell type to another The histone code hypothesis contends that precise patterns of chemical modifications of histones contain information that influences whether or not a particular gene is expressed Daughter cells inherit patterns of histone modification and thus patterns of gene expression from the parent cells This is an example of epigenetic inheritance patterns of inheritance that are not due to differences in gene sequences 2011 Pearson Education Inc Regulatory Sequences and Regulatory Proteins Eukaryotic promoters are similar to bacterial promoters There are three conserved sequences and each eukaryotic promoter has two of the three The most common sequence is the TATA box All eukaryotic promoters are bound by the TATA binding protein TBP 2011 Pearson Education Inc Some Regulatory Sequences Are Near the Promoter Promoter proximal elements are located just upstream of the promoter and the transcription start site and have sequences that are unique to specific genes providing a mechanism for eukaryotic cells to exert precise control over transcription 2011 Pearson Education Inc 2011 Pearson Education Inc Some Regulatory Sequences Are Far from the Promoter While exploring how human immune system cells regulate genes that produce antibodies Susumu Tonegawa and colleagues discovered that the intron rather than the exon contains a regulatory sequence required for transcription to occur The results were remarkable because 1 The regulatory