Summary
Genetics summary chapter 15 VU amsterdam
- Course
- Institution
This summary covers complete chapter 15 of genetics at the Vrije Universiteit Amsterdam.
[Show more]
Seller
Follow
ranayuksel2152
Content preview
Chapter 15 – gene regulation in eukaryotes 1: transcriptional and translation regulationEukaryotic cells need to adapt to environmental changes and stresses. Gene regulation is necessary to establish and
maintain the differences in structure and function among distinct cell types.
- Transcriptional factor: a category of proteins that influence the ability of RNA polymerase to transcribe DNA into
RNA. An important version are the transcriptional factors that affect the ability of RNA polymerase to begin the
transcription process. Two types of transcriptional factors that are needed:
1. General transcriptional factors – are required for the binding of RNA polymerase to the core promotor and
for progression of the elongation stage. They are necessary for any transcription to occur.
2. Regulatory transcription factors – eukaryotes have these and they serve to regulate the rate of transcription
of target genes.
Transcriptional factors recognize cis-acting elements that are located in the vicinity of the core promotor. These DNA
sequences are analogous to the operator sites found near bacterial promotors. Operator is a site where a regulatory
protein (inhibitor/activator) can bind and the promotor is the site where the RNA polymerase binds. In eukaryotes, these
DNA sequences are known as the regulatory sequences, control elements or regulatory elements.
Regulation of gene expression:
1. Transcription: the regulatory transcription factors can activate/inhibit transcription. The arrangements and
compositions of nucleosomes influence transcription. DNA methylation often inhibits transcription.
2. RNA processes (pre-mRNA): alternative splicing alters exon choices. RNA editing alters the base sequence of
mRNAs.
3. Translation: small RNAs (siRNAs and miRNAs) silence the translation of mRNA RNA interference. Proteins that
bind to the 5’ end of the mRNA regulate translation. mRNA stability may be influenced by RNA-binding proteins.
4. Posttranslational modifications: feedback inhibition and covalent modifications regulate protein function.
functional protein
When a regulatory transcription factors bind to the regulatory elements (Cis-regulatory elements (CREs) are regions of non-
coding DNA which regulate the transcription of neighbouring genes), it affects the transcription. Stimulating/enhancing
transcription activator the sequence it binds to is called the enhancer. Regulatory transcription factors that are
repressors (inhibit) the sequence it binds to is called thee silencer.
- Combinatorial control: eukaryotic genes are regulator by many factors. The combination of many factors
determines the expression of any given gene. This happens at transcriptional level:
1. One/more activator proteins may stimulate the ability of RNA polymerase to initiate transcription.
2. One/more repressor proteins may inhibit the ability of RNA polymerase to initiate transcription.
3. The function of activators/repressors may be modified due to binding of small effector molecules, protein-
protein interactions and covalent modifications.
4. Regulatory proteins may alter the composition or arrangement of nucleosomes in the vicinity of the
promotor, effecting transcription.
5. DNA methylation may inhibit transcription, either by preventing the binding of the activator protein or by
recruiting proteins that change the structure of chromatin in a way that inhibits transcription.
6. The formation of heterochromatin may inhibit gene expression in localized regions of a chromosome.
Transcriptional regulated is aimed at controlling the initiation of transcription at the promotor. Structural features of
regulatory transcription factors allow them to bind to DNA. General and regulatory transcription factors have regions
(domains) that have specific functions. When a domain/portion of the domain has a similar structure in many different
proteins (transcription factors), the structurally similar region is a motif.
The α helix structure is common in transcriptional regulatory factors (proteins) because it has a proper width to bind into
the major groove of the DNA double helix. In helix-turn-helix and helix-loop-helix motifs, an α helix called the recognition
helix makes contact with and recognizes a base sequence along the major groove of DNA. A major groove is a region of the
DNA double helix where the nucleotide bases are in contact with the water in the cellular fluid. Hydrogen bonding between
the amino acid side chains in an α helix and the nucleotide bases in the DNA is one way a transcription factor binds to a
specific DNA sequence. In addition, the recognition helix often contains positively charged amino acids, such as lysine and
arginine that interact with the DNA backbone which is negatively charged .
- Helix-turn-helix motif: two α helices (recognition helices) are connected by a turn. The α helices bind to the DNA
within the major groove.
- Helix-loop-helix motif: a short α helix is connected to a longer α helix by a loop. A dimer is formed from the
interaction of the α helices and the longer α helix is bound to the DNA.
- Zinc finger motif: A zinc finger motif is composed of an α helix and two β sheets that are held together by a zinc
(Zn2+) metal ion. The zinc finger can recognize DNA sequences within the major groove.
- Leucine zipper motif: this motif promotes dimerization. The leucine zipper and the helix-loop-helix mediate
protein dimerization. The two α helices (coiled coil) are intertwined due to the interactions between their
leucines, resulting in a protein dimerization.
, Chapter 15 – gene regulation in eukaryotes 1: transcriptional and translation regulation
a. Homodimer: two identical transcription factors that come together and form a homodimer.
b. Heterodimer: two different transcription factors can come together and form a heterodimer.
Regulatory transcription factors recognize regulatory elements that function as enhancers/silencers.
- Up regulation: regulatory element (site where the regulatory transcription factor (activator) the enhancers)
that stimulate transcription by 10 to 1000 fold.
- Down regulation: regulatory elements (silencers) that inhibit transcription.
Many regulatory elements are orientation-independent/bidirectional. They can function in the forward/reverse direction.
An example:
5’ – GATA – 3’ 5’ – TCAT – 3’
3’ – CTAT – 5’ 3’ – ATAG – 5’
Regulatory elements are often located in a region within 200 bp upstream from the core promotor. However, they can be
quite distant, yet exert strong effects on the ability of RNA polymerase to initiate transcription at the core promoter. In
some cases, regulatory elements are located downstream from the promotor site and may be found in introns, the
noncoding parts of the genes. Upstream = left and downstream = right. Regulatory elements may exert their effects through
TFIIID or mediator.
1. Regulation via TFIID: some regulatory transcription factors bind to a regulatory element and then influence the
function of the TFIID. TFIID is a general transcription factor that binds to the TATA box and is needed to recruit
RNA polymerase II to the core promoter. Activator regulatory factors can enhance the ability of TFIID to initiate
transcription. The activator proteins might help TFIID to bind to the TATA box or they might enhance the function
of the TFIID in a way that facilitates its ability to recruit RNA polymerase II. In some cases, activator regulatory
transcription factors might exert their effects by interacting with coactivators – proteins that increase the rate of
transcription but do not directly bind to the DNA itself. Coactivators contain a transactivation domain that
promotes the activation of RNA polymerase by interacting with general transcription factors.
Repressor regulatory transcription factors might bind to the silencers and inhibit the function of TFIID. They could
exert their effects by preventing the binding of TFIID to the TATA box or by inhibiting the ability of TFIID to recruit
RNA polymerase II to the core promotor.
2. Regulation via mediator: a 2nd way that regulatory transcription factors control RNA polymerase II is via mediator:
a protein complex that mediates the interaction between RNA polymerase II and regulatory transcription factors.
A mediator controls the ability of RNA polymerase II to progress to the elongation stage via phosphorylation of
the carboxyl-terminal domain (CTD). Activator regulatory factors enhance the ability of the mediator to cause
phosphorylation of the CTD and thereby facilitates the switch between initiation and elongation.
3. Regulation via changes in chromatin structure: a 3rd way that regulatory transcription factors influence
transcription is by recruiting certain proteins which affect nucleosome positions and compositions, to the
promotor region and thereby altering chromatin structures.
The functions of regulatory transcription factor proteins are controlled in 3 ways:
1. The binding of a small effector molecule – a small effector molecule may bind to the regulatory transcription
factors and thereby promote its binding to the DNA steroid hormones.
2. Protein-protein interactions – the formation of homodimers and heterodimers
3. Covalent modifications – attachment of a phosphate group for example. Phosphorylation of the activators can
control their ability to stimulate transcription.
Steroid hormones act as small effector molecules that bind to the regulatory transcription factors and thereby facilitates its
binding to the DNA. This type of transcription factor is known as a steroid receptor, because the steroid hormone binds
directly to the regulatory transcription factor protein. The binding of the steroid receptor to the regulatory protein
increases the rate of gene transcription. In animals, steroid hormones act as signaling molecules that are synthesizes by
endocrine glands and secreted into the bloodstream. The hormones are then taken up by cells that respond to these
substances in different ways. For example, glucocorticoid hormones influence nutrient metabolism in most body cells.
Other steroid hormones (estrogen and testosterone) are called gonadocorticoids because they influence the function of the
gonads.
The glucocorticoid hormone binds to the glucocorticoid receptor inside the cell. Prior to this binding, the glucocorticoid
receptor is complexed with proteins called the heat shock proteins (HSP). After the hormone binds to the receptor, the HSP
protein is released, thereby exposing a nuclear localization sign (NLS) – a sequence of amino acids within the protein that
directs the protein into the nucleus. Two glucocorticoid receptors form a homodimer and then travel though a nuclear pore
into the nucleus. In the nucleus, the glucocorticoid receptor homodimer binds to the DNA sites with the following
consensus sequence:
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller ranayuksel2152. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $6.98. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
52510 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now