Chapter 13

Effect of an activator via TFIID, a general transcription factor

1- An activator binds to an enhancer 2- The activator enhances the ability of a GTF called TFIID to bind to the TAT box 3- TFIID promotes the assembly of the pre initiation complex

Gene Regulation Occurs at Different Points in the Process from DNA to Protein

In bacteria, gene regulation most commonly occurs at the level of transcription, which means that bacteria regulate how much mRNA is made from genes. In eukaryotes, gene regulation occurs at many levels, including transcription, RNA processing, translation, and after translation is completed.

Differences in regulation of transcription in eukaryotes from bacteria:

In eukaryotic species: Genes are almost always organized individually. Eukaryotic gene regulation tends to be more intricate.

How do living organisms benefit from gene regulation?

It conserves energy. Also ensures that genes are expressed in the appropriate cell types and at the correct stage of development

Open conformation

Such chromatin, said to be in an open conformation, is accessible to GTFs and RNA polymerase II so transcription can take place.

Overview of gene regulation in (a) bacteria and (b) eukaryotes

(a) Bacterial gene regulation: Transcription, Translation, Post-translatoin (b) Eukaryotic gene regulation: Transcription, RNA processing, Translation, Post-translation

What are the effects of covalent modifications of histones?

-Modifications may directly influence interactions between DNA and histone proteins, and between adjacent nucleosomes. -Histone modifications provide binding sites that are recognized by other proteins. "Histone Code Hypothesis"- the pattern of histone modification is recognized by proteins much like a language or code. (May attract proteins that inhibit or promote gene transcription)

How do ATP-dependent chromatin-remodeling complexes change chromatin structure? Three effects are possible:

-These complexes may bind to chromatin and change the locations of nucleosomes -Remodeling complexes may evict histone octamers from the DNA, thereby creating gaps where nucleosomes are not found -Chromatin-remodeling complexes may change the composition of nucleosomes by removing standard histone proteins from an octamer and replacing them with histone variants.

Gene Regulation of lactose utilization in E.Coli

1- Lactose becomes available in the environment of the bacterium 2- Due to gene regulation, thebacterium increases production of the lactose perm ease and B-galactosidase proteins. 3- The bacterium readily uses the lactose until it is gone 4- Most proteins involved with the use of lactose are degraded

Eukaryotic Structural Genes Have a

Core Promoter and Regulatory Elements

Closed conformation

Depending on the locations and arrangements of nucleosomes, a region containing a gene may be in a closed conformation, and transcription may be difficult or impossible.

Bacteria Regulate Genes to Respond to Changes in Their Environment

E. coli carries genes that code for proteins that enable it to take up lactose from the environment and metabolize it. In order to utilize lactose, E.coli requires a transporter, called lactose perm ease, that facilitates the uptake up lactose into the cell, and an enzyme, called B-galactosidase, that catalyzes the breakdown of lactose. Gene regulation conserves energy because it ensures that the proteins needed for lactose utilization are made only when lactose is present in the environment.

Eukaryotic Gene Regulation Enables Multicellular Organisms to Proceed Through Developmental Stages

Gene regulation ensures that the correct hemoglobin protein is produced at the right time in development. (Hemoglobin is a protein that delivers oxygen to the cells of a mammal's body. Composed of four globin polypeptides, two encoded by one globin gene and two encoded by another globin gene)

Constitutive Genes

Genes that have relatively constant levels of expression in all conditions over time. (ex. Genes that encode proteins that are always required for the survival of an organism, such as certain metabolic enzymes)

Histone Modifications Affect Gene Transcription

Histone acetyltransferase- an enzyme that attaches acetyl groups (-COCH3) to the amino terminal tails of histone proteins. When acetylated, histone proteins do not bind as tightly to the DNA, which aids in transcription.

Histone Variant

a histone protein that has a slightly different amino acid sequence from the standard histone proteins described in Ch.11. Some histone variants promote gene transcription, whereas others inhibit it.

As in bacteria, eukaryotic proteins can be regulated in a variety of ways other than gene regulation, including:

cellular regulation and biochemical regulation (such as feedback inhibition)

Activators and Repressors May Influence the Function of GTFs of Mediator

coactivator- a protein that increases the rate of transcription but does not directly bind to the DNA itself. GTF called transcription factor II D (TFIID) recognizes the TATA box and begins the assembly process.

Mediator

is composed of many proteins that bind to each other to form an elliptically shaped complex that partially wraps around RNA polymerase II and the GTFs. It mediates interactions between the preinitiation complex and regulatory transcription factors such as activators or repressors that bind to enhancers or silencers. The function of mediator is to control the rate at which RNA polymerase can begin to transcribe RNA at the transcriptional start site.

Enhancers

regulatory element that plays a role in the ability of RNA polymerase to begin transcription, thereby enhancing the rate of transcription.

Silencers

regulatory element that prevent transcription of a given gene when its expression is not needed.

Gene Regulation

the ability of cells to control the expression of their genes.

Effect of an activator via mediator

1- Mediator binds to the preinitiation complex, but transcriptional initiation does not occur 2- An activator binds to a distant enhancer and a coactivator binds to the activator. A bend in the DNA allows the activator/coactivator complex to interact with mediator. This interaction causes RNA polymerase to proceed to the elongation stage of transcription.

At the level of transcription, common factors that contribute to combinatorial control include the following:

1. One or more activators may stimulate the ability of RNA polymerase to initiate transcription. 2. One or more repressors may inhibit the ability of RNA polymerase to initiate transcription. 3. The function of activators and repressors may be modulated in several ways, which include the binding of small effector molecules, protein-protein interactions, and covalent modifications. 4. Activators are necessary to alter chromatin structure in the region where a gene is located, thereby making it easier for the gene to be recognized and transcribed by RNA polymerase. 5. DNA methylation usually inhibits transcription, either by preventing the binding of an activator or by recruiting proteins that inhibit transcription.

Transcription Is Controlled by Changes in Chromatin Structure

ATP-dependent chromatin-remodeling complexes: which are a group of proteins that alter chromatin structure. They use energy from ATP hydrolysis to drive a change in the locations and/or compositions of nucleosomes, thereby making the DNA more or less amenable to transcription.

Preinitiation complex

The completed assembly of RNA polymerase II and GTFs at the TATA box

Cell differentiation

The process by which cells become specialized into particular types.

Eukaryotic Gene Regulation Produces Different Cell Types in a Single Organism

The three cell types shown in Figure 13.2 contain the same genome, meaning they carry the same set of genes. However their proteomes- the collection of proteins they make- are quite different. (Gene regulation plays a major role in determining the proteome of each cell type)

Combinatorial Control

the combination of many factors determines the expression of any given gene.

Basal Transcription

the core promoter, by itself, results in a low level of transcription.

Gene Expression

the process by which the information within a gene is made into a functional product, such as an RNA molecule or a protein.

When geneticists say a gene is "turned off," they mean that very little or no mRNA is made from that gene,

whereas a gene that is "turned on" is transcribed into mRNA.

For eukaryotic structural genes that encode proteins, three features are common amongst most promoters:

Regulatory elements, a TATA box, and a transcriptional start site. (The TATA box and transcriptional start site form the core promoter) The transcriptional start site is- the place in the DNA where transcription actually begins. The TATA box- is important in determining the precise starting point for transcription. Regulatory elements- are DNA segments that regulate eukaryotic genes.

RNA Polymerase II, General Transcription Factors, and Mediator Are Needed to Transcribe Eukaryotic Structural Genes

Three types of proteins that play a role in initiating transcription at the core promoter of structural genes: RNA polymerase II, five different proteins called general transcription factors (GTFs), and a large protein complex called mediator. RNA polymerase II and GTFs must come together at the TATA box of the core promoter so the transcription can be initiated. RNA polymerase II binds to the DNA.