Chapter 19- Control of Gene Expression in Eukaryotes

19.1 Gene Regulation in Eukaryotes- An Overview

• In eukaryotes, DNA is wrapped around proteins to create a structure called chromatin. 
• Biologists say that chromatin remodeling must occur before transcription, transitioning from a condensed or “closed” state to a decondensed or “ open ” state.
• RNA processing is the steps required to produce a mature, processed mRNA from a primary RNA transcript.
• ==mRNA stability is regulated in eukaryotes.== 

19.2 Chromatin Remodeling 

• A group of proteins called histones are the most abundant DNA-associated proteins. 
• ==Chromatin consists of DNA complexed with histones and other proteins.==
• In some preparations for electron microscopy, chromatin looked like beads on a string. The “beads” came to be called nucleosomes.
• ==DNA and histones must be altered for RNA polymerase to make contact with DNA==. 
• ==The central idea is that chromatin must be decondensed to expose the promoter so RNA polymerase can bind to it.== 
• A group of enzymes known as DNA methyltransferases add methyl groups (-CH3) to cytosine residues in DNA, by a process called DNA methylation.
• Researchers have proposed that particular combinations of histone modifications on specific amino acids of histone proteins set the state of chromatin condensation for a particular gene which is known as the histone code hypothesis.
• Histone acetyltransferases (HATs) add acetyl groups to the positively charged lysine residues in histones.
• Histone deacetylases (HDACs) remove them.
• Histone acetylation usually promotes decondensed chromatin, a state associated with active transcription. 
• Another major player in chromatin alteration and gene regulation are proteins that form macromolecular machines called chromatin-remodeling complexes. These complexes harness the energy in ATP to reshape chromatin.
• Epigenetic inheritance is the collective term for any mechanism of inheritance that is due to something other than differences in DNA sequences. 

19.3 Initiating Transcription 

• In eukaryotes the term core promoter is often used to indicate the specific sequence where RNA polymerase binds, as opposed to the other sequences needed for regulation of transcription.
• The most intensively studied core promoter sequence is a short stretch of DNA known as the TATA box.
• Once a core promoter that contains a TATA box has been exposed by chromatin remodeling, the first step in initiating transcription is binding of the TATA-binding protein (TBP).  
• Regulatory sequences allow the binding of proteins that control the initiation of transcription. 
• Regulatorγsequences such as the ones discovered in yeast that are close to the promoter are termed promoter-proximal elements. 
• Enhancers are regulatory DNA sequences primarily found in eukaryotes. When regulatory proteins called transcriptional activators, or activators for short, bind to enhancers, transcription begins.
• Eukaryotes also possess regulatory sequences that are similar in structure and share key characteristics with enhancers but work to inhibit transcription which are called silencers.
• When regulatory proteins called repressors bind to silencers, transcription is shut down.
• General transcription factors are proteins that interact with the core promoter and are not restricted to particular genes or cell types.
• A large complex of proteins called the Mediator acts as a bridge between regulatory transcription factors, general transcription factors, and RNA polymerase II.
• ==Activators work not only to stimulate transcription but also to bring chromatin remodeling proteins to the right place at the right time==. 
• Any regulation that occurs after transcription is a form of post-transcriptional control. These regulatory mechanisms include:
  • different ways of splicing the same primary transcript
  • altering the ability to translate particular mRNAs, or destroying them
  • altering the activity of proteins after translation has occurred. 
•  Splicing the same primary RNA transcript in different ways is alternative splicing. 
• ==Alternative splicing is controlled by proteins that bind to RNAs in the nucleus and interact with spliceosomes to influence which sequences are used for splicing==
• RNA interference (RNAi) occurs when a tiny, single stranded RNA held by a protein complex binds to a complementary sequence in another RNA.
• One form of RNA interference works through a small RNA called a microRNA (miRNA) that is derived from transcription of cellular genes
• A macromolecular machine called the proteasome recognizes proteins that have a ubiquitin tag and cuts them into short segments.

19.4 Post-Transcriptional Control 

• Each type of cancer is caused by a different set of mutations that lead to cancer when they alter two classes of genes:
  • genes that stop or slow the cell cycle
  • genes that trigger cell growth and division. 

19.5 Linking Cancer to Defects in Gene Regulation 

• Proteins that stop or slow the cell cycle when conditions are unfavorable for cell division are called tumor suppressors.
• Genes that stimulate cell division are called proto-oncogenes 
• Oncogene is a mutant allele that promotes cancer

19.6 A Comparison of Gene Expression in Bacteria and Eukaryotes

• There are many differences between the control of gene expression in bacteria and in eukaryotes: 
  • DNA packaging
  • Complexity of transcription 
  • Coordinated transcription 
  • Reliance on post-transcriptional control

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