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Gene Regulation GENE REGULATION in Eukaryotic Cells Every cell in a multi-cellular eukaryote has a copy of all genes. However, different genes are actively expressed in different cells Chapter 15 Gene Regulation 1 Gene Regulation Eukaryotic Regulation A variety of mechanisms Five primary levels of control: Nuclear levels Chromatin Packing Transcriptional Control Posttranscriptional Control Cytoplasmic levels Translational Control Posttranslational Control Chapter 15 Gene Regulation 2 Regulation of Gene Expression: Levels of Control in Eukaryotes 3 Chromatin Structure Eukaryotic DNA associated with histone proteins Together make up chromatin As seen in the interphase nucleus Nucleosomes: Gene Regulation DNA wound around balls of eight molecules of histone proteins Looks like “beads on a string” Each bead a nucleosome The levels of chromatin packing determined by degree of nucleosome coiling Chapter 15 Gene Regulation 4 Levels of Chromatin Structure 5 Gene Regulation Chromatin Packing Euchromatin Loosely coiled DNA Transcriptionally active Heterochromatin Tightly packed DNA Transcriptionally inactive Barr Bodies Chapter 15 Females have two X chromosomes, but only one is active Other is tightly packed along its entire length Inactive X chromosome is Barr body Gene Regulation 6 X-Inactivation in Mammalian Females 7 8 Non-Coding DNA • 97% of human DNA is non-coding • Repetitive DNA not in genes • Tandemly repetitive DNA short sequences repeated in series DNA Methylation The attachment of methyl groups to DNA bases Inactivates the genes Demethylating certain inactive genes turns them on. 9 Histone Acetylation Acetyl groups attaching to histones Acetylated histones grip DNA less tightly allowing for transcription to occur more easily 10 Gene Regulation Transcriptional Control Transcription controlled by proteins called transcription factors Chapter 15 Bind to enhancer DNA Regions of DNA where factors that regulate transcription can also bind Always present in cell, but most likely have to be activated before they will bind to DNA Gene Regulation 11 Initiation of Transcription 12 Gene Regulation Posttranscriptional Control Posttranscriptional control operates on primary mRNA transcript Given a specific primary transcript: Excision of introns can vary Splicing of exons can vary May also control speed of mRNA transport from nucleus to cytoplasm Chapter 15 Determines the type of mature transcript that leaves the nucleus Will affect the number of transcripts arriving at rough ER And therefore the amount of gene product realized per unit time Gene Regulation 13 Processing of mRNA Transcripts 14 Gene Regulation Translational Control Translational Control - Determines degree to which mRNA is translated into a protein product Presence of 5′ cap Length of poly-A tail on 3′ end Posttranslational Control - Affects the activity of a protein product Chapter 15 Activation Degradation rate Gene Regulation 15 Gene Regulation Chapter 15 http://www.sciencemag.org/cgi/con tent/full/319/5871/1781b Gene Regulation 16