Chapter 18: Regulation of Transcription in Eukaryotes
Chapter 18: Regulation of Transcription in Eukaryotes Biol 2311
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This 3 page Class Notes was uploaded by Rachael Couch on Friday November 20, 2015. The Class Notes belongs to Biol 2311 at University of Texas at Dallas taught by John Burr in Fall 2014. Since its upload, it has received 34 views.
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Date Created: 11/20/15
Chapter 18: Control of Gene Expression in Eukaryotes Animal cells can be controlled on the level of 1. Chromatin remodeling 2. Splicing of the primary RNA transcript 3. mRNA stability 4. Posttranslational modifications Transcriptional Control in Eukaryotes vs Prokaryotes Bacteria has a promoter that consists of the “pribnow box” (10 region) and the 35 region”. In most bacterial genes, the promoter is all that is necessary for RNA polymerase to sit down on the DNA and begin transcription. Eukaryotic RNA polymerase does not bind to its promoter (transcription does not occur) without the assistance of other proteins. Eukaryotic Promoters Eukaryotic promoters have a sequence that resembles the Pribnow box called a TATA box located 25 to 35 to the transcription start site. RNA polymerase cannot directly bind to the promoter (the TATA box), instead, a protein called TBP (TATA boxbinding protein) binds at the promoter site. o TBP induces a sharp bend in the DNA o TBP is a subunit of a protein complex called TFIIID TFIIID = [TBP + 13 “TAF” proteins (TBPAssociated Factors)]. After TFIID binds to the TATA box and bends the DNA, a set of additional proteins (TFIIA, TFIIA, TFIIE, TFIIH) are recruited to the promoter. These proteins are called general transcription factors. Once the general transcription factors have assembled on the promoter, RNA polymerase can bind. Activator Proteins The assembly of the general transcription factors on the promoter requires assistance of additional gene regulatory proteins called transcriptional activators These proteins bind adjacent to the promoter (promoter proximal elements) or at more distant locations (enhancers) Activator proteins can assist in the assembly of general transcription factors on the promoter even though they are so far away due to the flexibility of DNA. The activator at enhancer sites binds comes in direct contact to help assemble transcription factors because the DNA can bend to make a loop to allow it to do so. Most often the interaction between the activator proteins and the general transcription factors involves a protein complex called a mediator Chromatinremodeling proteins and histone acetylases act to modify the nucleosome structure Chromatin Eukaryotic DNA wraps around histone proteins to form nucleosomes. The combination of DNA and histones is called chromatin Chromatin can exist both in an extended “beads on a string” state and in more condensed forms, most specifically a form called the 30nm fiber o The 30nm fiber is the basic state of most chromatin in the cells Genes are inaccessible for transcription in a 30nm fiber o Accessible in the “beadsonastring” form Chromatinremodeling proteins and histone acetylases act to convert chromatin in the 30nm form to the more accessible “beadsonastring” form, which permits the binding of transcriptional activators and permits RNA polymerase to transcribe Also, Chromatinremodeling complexes o 1) Reposition the nucleosome on the DNA (often exposing enhancer sites) o 2) Loosen the DNA on the nucleosomes for RNA polymerase Other chromatin remodeling complexes return the nucleosomes back to their standard state when gene expression is finished Histones and nucleosomes Nucleosome = core of 8 histone proteins: 2 each of histones H2A, H2B, H3, and H4 Each of the 4 types of histone protein that form the octameric core of a nucleosome has it amino terminus “waving free”. These “free waving” amino terminal segments are rich in the positively charged amino acid lysine These lysines in the aminoterminal histone segments are what can become acetylated by the histone acetlyases Acetylation of these lysines has several functions in gene activation, including unpacking of the 30nm fiber, and also recruiting general transcription factors such as TFIID once the fibers have been unpacked Acetylation of histone lysines by histone acetyl transferases (HATs) is associated with decondensing chromatin and making genes accessible for transcription o Acetylation = activation Removing these acetyl groups from the histones, by histone deacetylases (HDACs), silence gene expression by repacking the nucleosomes back into 30 nm fibers Alternative RNA splicing Another aspect of regulation gene expression in eukaryotes Different proteins are encoded by a single gene but the primary RNA transcript is spliced differently in the two different cell types to produce 2 mRNAs o Different mRNAs different (but related) proteins Ex: The expression of two different versions of the protein tropomysin in skeletal muscle versus smooth muscle RNA interference (micro RNAs) miRNA molecules act to target certain mRNA molecules (to which they are complementary in sequence) for rapid degradation There are several hundred genes that encode miRNA molecules, that have evolved to target specific mRNAs in the cytosol, thereby limiting the lifetime of these mRNAs and limiting expression of the protein encoded by the target mRNA. These miRNAs initially form a hairpin structure which is trimmed in the nucleus, then exported to the cytosol, where the loop at the end is cleaved, yielding ultimately a 22 nucleotide long doublestranded mature miRNA molecule. In the cytosol the RISC complex (a set of proteins) binds the doublestranded miRNA, removing one of the strands. The remaining strand is complementary to a sequence on the target mRNA. The miRNARISC complex then binds the target mRNA, and a ribonuclease component of the RISC complex cleaves the mRNA. If there is an imperfect match between the miRNA and the mRNA, the mRNA is not cleaved, but the RISCmiRNA complex remains bound to the mRNA, thereby inhibiting its translation.