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