GENETICS: Chapter 15: Gene Regulation in Eukaryotes I: Transcriptional Regulation

Regulatory transcription factors that bind to (1)___________ and increase transcription rates are called activators; in contrast, repressors bind to (2) and inhibit transcription

(1) enhancers (2) silencers

Why does acetylation loosen the DNA around octamers?

With the enzyme Histone acetyltransferase, it adds acetyl groups in order to disrupt the positive charges on the histone

Epigenetic

is the study of mechanisms that lead to changes in gene expression (does not change the sequence) that... -can be passed from cell to cell -are reversible -do not involve a change in the DNA sequence -are long-term (not just temporarily on/off)

Glucocorticoid can pass through the membrane because...

it is hydrophobic

What are the names of the structures with lines and question marks

light orange blank: Activator dark orange blank: Enhancer yellow blank: repressor protein

DNA methylation: Where do many genes contain CpG islands?

near/in their promoters —1000-2000 nucleotides long and contain many CpG sites —in housekeeping genes, the CpG islands remain unmethylated —in tissue-specific genes, methylation may turn the gene "OFF"

The term epigenetic inheritance is used when these changes are... What is an example of epigenetic inheritance? And an epigenetic change that is not an example of epigenetic inheritance?

passed on from parent to offspring -ex. imprinting -not an example: a lung cell that has undergone an epigenetic modification that pushes it towards cancer

Epigenetic changes include....

1. Chromatin Remodeling (histone variants and change in nucleosomes) 2. Histone Modification 3. DNA Methylation (put methyl groups onto DNA)

Test Your Understanding: We learned that bacteria can control the expression of several genes that work in a common pathway through the use of operons. However, eukaryotic cells do not have operons. Based on what we've just learned, is there any way that these cells could still control a set of genes that work in a common pathway? (This is important!)

1. same enhancer sequence for all of the genes involved (they're all tied to same enhancer or repressor) If those three genes have the same enhancer sequence they just have to produce the same activator. And if they have the same pathway, they will all activate together.

What do you think activators/repressors actually do to influence the rate of transcription?

Activators have to do something to help RNA polymerase to bind better ex) provide a nice binding site for the other transcriptional factor Repressors will do something to block the process!

Histone Modification: How is the pattern of histone modifications is like its own "genetic code?"

By altering how the histones interact with each other, with the DNA or with other proteins

DNA methylation: What is it carries out by? What enzyme?

Carried out by the enzyme DNA methyltransferase -Is common in some eukaryotic species, but not all

Chromatin Remodeling: Importantly, chromatin-remodeling complexes can catalyze reactions in what direction?

EITHER DIRECTION (thereby increasing or decreasing compaction)

Glucocorticoid Response Elements (GREs) are located near dozens of different genes, so the hormone can...

activate many genes simultaneously

Chromatin-Remodeling Complexes

are a diverse group of proteins that create local or large-scale changes in nucleosome positioning -require ATP and utilize a DNA translocase subunit to move along DNA -ex. the "SWI/SNF-family"

General Transcription Factors

are needed to recruit RNA polymerase to the core promoter for all genes

Transcription Factors

are proteins that influence the ability of RNA polymerase to transcribe a gene

What do Regulatory Transcription Factors bind to?

bind to DNA segments called regulatory elements (regulatory sequences) -usually located in the -50 to -100 region but can also be far from the promoter and even in downstream regions or within introns! -can be enhancers or silencers

Regulatory Transcription Factors

exist to regulate only a certain number of target gene(s) -exhibit an incredible diversity -2-3% of the genes in the human genome encode for transcription factors! -You know them as activators and repressors

Histone Modification: Histone acetylation and histone methylation

histone acetylation normally opens up the chromatin for transcription (increase expression); histone methylation often does the opposite

DNA methylation

is a change in chromatin structure that almost always silences gene expression

Chromatin Remodeling: Activator and repressor proteins can recruit different types of chromatin-remodeling complexes to what region of a gene?

the promoter region of a gene

DNA methylation: How can DNA methylation usually inhibit the transcription of eukaryotic genes?

—can either block activating proteins from binding to the promoter or recruit transcriptionally-repressive proteins —ex. it might recruit a histone deacetylase enzyme

What kind of regulatory protein is glucocorticoid receptor?

-Protein is an activator

The three mechanisms of Chromatin-Remodeling:

1. Change in nucleosome position 2. Histone eviction 3. Replacement with histone variants

What kind of regulatory element is the GRE?

GRE (DNA part) is an enhancer

Chromatin Remodeling: How would gene expression be affected in a region that has evicted a histone?

Gene expression would also most likely increase in this case because it creates a more open confirmation. The transcription factors will be able to get in easier!

Chromatin Remodeling: How would gene expression be affected in a region that has a change in the spacing of a nucleosome over a long distance?

Gene expression would most likely increase because it is more open now because of the spacing. The transcription factors will be able to get in easier!

What is a specific example of finer modulation?

Glucocorticoid receptors

Chromatin Remodeling:True or False? Chromatin can be in the open conformation or the closed conformation, making it either more amenable or less amenable to transcription, respectively

TRUE

Histone Modification: Why does removing acetyl groups tighten the DNA around octamers?

With the enzyme Histone deacetylase. This decreases transcription (therefore, decrease gene expression)

Some regulatory transcription factors are _____________ for certain steroid hormones that are secreted into the circulatory system. What type of receptor is an example of this?

receptors •ex. Glucocorticoid receptors are bound by glucocorticoid and promote the transcription of genes needed for glucose utilization, fat mobilization and protein breakdown (also transcription factors and get activated because they are also receptors)

Histone Modification: Examples of histone modifications

•p = phosphate •ac = acetyl group •m = methyl group