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Genetics EXAM 3 > Chapter 11 - Eukaryote Gene Expression Control > Flashcards

Chapter 11 - Eukaryote Gene Expression Control Flashcards

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1
Q

Key to Eukaryotic Complexity

A

The complexity of eukaryotes is due to fine-tuned regulation of gene expression, not more genes.

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2
Q

Coding DNA vs. Regulatory DNA

A

Only about 2% of the human genome codes for RNA or protein; the remaining ~25% contains cis-acting elements that regulate gene expression.

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3
Q

Housekeeping Genes

A

Housekeeping genes are constitutively expressed (always on) because they are essential for basic cellular functions, such as energy metabolism and protein synthesis.

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4
Q

Tissue-Specific Genes

A

Some genes are expressed only in specific cell types or under certain conditions (e.g., hemoglobin in red blood cells, myoglobin in muscle cells).

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5
Q

Levels of Gene Expression Regulation

A

Gene expression can be regulated at the level of transcription, RNA processing, translation, and post-translational modifications.

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6
Q

Trans-acting Factors

A

Trans-acting factors are proteins (often transcription factors) that regulate gene expression by interacting with cis-acting elements.

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7
Q

Cis-acting Elements

A

Cis-acting elements are DNA sequences (promoters, enhancers, silencers) that control gene expression at specific locations.

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8
Q

Regulation at Transcription Level

A

Most eukaryotic gene expression regulation occurs at the transcription level, through interactions between trans-acting factors and cis-acting elements.

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9
Q

Gene Expression Layers

A

Gene expression is regulated at multiple levels: DNA level, transcription, RNA processing, translation, post-translational modifications, and protein stability.

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10
Q

Gene/DNA Level Regulation

A

Promoters, enhancers, silencers, and insulators control transcription initiation and gene expression.

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11
Q

Transcription Regulation

A

Transcription factors and co-activators bind to cis-acting elements in DNA. Epigenetic modifications (like DNA methylation) and chromatin remodeling affect transcription.

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12
Q

RNA Processing & Stability

A

Includes splicing, 5’ capping, polyadenylation, and RNA export. RNA stability (mRNA half-life) controls how long RNA is available for translation.

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13
Q

Translational Regulation

A

Translation initiation and speed of translation regulate protein production. Regulatory elements (like UTRs) can influence translation efficiency.

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14
Q

Protein Activation

A

Post-translational modifications (e.g., phosphorylation, acetylation) activate/inactivate proteins. Subcellular location of proteins regulates their function.

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15
Q

Protein Stability

A

Protein half-life varies—some proteins are very stable, while others are rapidly degraded.

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16
Q

Function of RNAs

A

mRNA serves as a template for translation. Non-coding RNAs (miRNA, siRNA) regulate gene expression at transcriptional/post-transcriptional levels.

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17
Q

Types of RNA Polymerase

A

-RNA Pol I: Transcribes rRNA genes.
- RNA Pol II: Transcribes mRNA (protein-coding genes).
- RNA Pol III: Transcribes tRNA genes.

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18
Q

Cis-acting Elements

A
  • Promoters: Directly involved in transcription initiation.
  • Enhancers: Increase transcription from a distance.
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19
Q

Core Promoter

A

-Contains TATA box, CAAT box, and CpG islands.
- Basal transcription factors bind to this region to recruit RNA Pol II.

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20
Q

TATA Box

A
  • A conserved sequence (TATAAT) found around -30 from the transcription start site. Important for RNA Pol II binding.
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21
Q

CAAT Box

A
  • A conserved sequence often found upstream of the TATA box that is involved in transcription regulation.
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22
Q

CpG Islands

A

-Regions rich in CG dinucleotides, often located near promoters and involved in gene regulation.

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23
Q

Basal Transcription Factors

A
  • TBP binds to TATA box.
  • TAFs bind to TBP and recruit RNA Pol II. This forms the pre-initiation complex.
  • Allows for low basal transcription.
  • proteins that are essential for gene transcription to occur
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24
Q

Enhancers

A
  • DNA sequences that regulate gene expression by binding transcription factors (TFs).
  • Act as either activators or repressors.
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25
Core Promoter vs Enhancers
- Core promoter: Same for all genes of a given RNA polymerase type, includes basal transcription factors (basal machinery). - Enhancers are gene-specific and have unique TF binding sites
26
Location of Enhancers
- Enhancers can be upstream, downstream, or within introns of the gene they regulate. - They can act over kilobases (kb) away from the promoter.
27
Multiple Promoters
- One enhancer can regulate multiple promoters/genes unless insulators prevent interaction.
28
Function of TFs in Enhancers
- Activators: Bind to enhancers to enhance transcription. - Repressors: Bind to enhancers to decrease transcription.
29
Transcriptional Activators
- Bind to specific DNA sequences (motifs) in enhancers. - Often referred to as consensus sequences or binding sites.
30
Role of Activators
- Increase transcription by promoting the assembly of the transcription machinery. - Recruit mediators and co-activators.
31
Mediators and Co-activators
- Mediators bridge TFs and basal transcription machinery (RNA polymerase II). - Co-activators help bring enhancers and promoters together.
32
DNA Bending by Co-activators
- Most co-activators bend the DNA to facilitate the interaction between enhancers and promoters.
33
Chromatin Remodeling by Co-activators
- Some co-activators perform histone modification (usually histone acetylation through HATs). - Nucleosome shuffling exposes the promoter.
34
Transcriptional Repressors
- Bind to specific sites within enhancers. - Inhibit gene expression by preventing the recruitment of transcription machinery.
35
Co-repressors
- Recruited by repressors. - Block transcription in two ways: 1) Disrupt basal machinery. 2) Remodel chromatin (via HDACs).
36
Chromatin Remodeling by Co-repressors
- Histone deacetylases (HDACs) remove acetyl groups from histones, making the chromatin more tightly packed, thus reducing transcription.
37
Indirect Repression Mechanisms
- Competition with activators: Repressors compete with activators for binding sites. - Direct binding to activators: Repressors block activators.
38
Dual Role of Transcription Factors
Some transcription factors can act as both activators and repressors, depending on the context (such as the presence of co-factors).
39
Sequence Motifs
- Proteins bind to DNA at specific “motifs” Not an exact sequence, but a series of “preferences” Some bp positions are strict, others are flexible You will often hear “consensus sequence,” this is a BAD concept
40
Nuclear Receptors
- Hydrophobic hormones (e.g., steroid hormones, thyroid hormones, vitamin D) bind to nuclear receptors inside the cell.
41
Hormone Binding
- Hormones bind to nuclear receptors, causing a conformational change that activates the receptor.
42
Dimers
- Upon hormone binding, nuclear receptors often form dimers (homo- or hetero-dimers).
43
Response Elements
- Dimers bind directly to specific DNA motifs called response elements, typically in the promoter/enhancer regions of target genes.
44
Activators vs. Repressors
- Nuclear receptors can act as activators or repressors based on the proteins they recruit. - Activators enhance transcription, while repressors block it.
45
Insulators
- DNA sequences that block enhancer-promoter interactions. - Organize DNA into loops.
46
Insulator Sequence Example
- CCGCGNGGNGGCAG is the binding site for CTCF (CCCTC-binding factor).
47
Function of Insulators
- Form boundaries for an enhancer’s effects. - Prevent spreading of heterochromatin into active gene regions.
48
DNA Loops
- An enhancer and promoter must be in the same loop to interact. - Loops are the units of transcriptional regulation by enhancers.
49
CTCF Binding and Loop Formation
- CTCF binds to insulator sequence and forms a loop by interacting with other distant CTCF proteins. - This looping regulates enhancer-promoter interactions
50
Noncoding RNAs (ncRNAs)
- RNAs that do not code for proteins. - Regulate gene expression and other cellular functions. - Majority of RNA in a cell is ncRNA.
51
Long Noncoding RNAs (lncRNAs)
- >200bp in length. - Involved in gene regulation, many with unknown functions. - Example: Xist (X-inactivation, Barr body formation).
52
Short Noncoding RNAs (<200bp)
- miRNAs: Regulate gene expression via RNA interference (RNAi). - siRNAs: Similar to miRNAs, also involved in RNAi. - piRNAs: Silence transposable elements in germline cells.
53
Other Short ncRNAs
- snoRNAs: Involved in rRNA maturation and ribosome assembly. - snRNAs: Involved in mRNA splicing. - tRFs: Derived from tRNAs, function still under investigation.
54
RNA Interference (RNAi)
- miRNAs and siRNAs induce gene silencing through degradation or translation inhibition of target mRNAs.
55
RNA Interference (RNAi)
- A process of gene silencing through inhibition of translation or mRNA degradation. - Involves miRNAs and siRNAs. - A major mechanism of post-transcriptional regulation.
56
miRNAs
- Derived from long primary RNA (pri-miRNA), processed into shorter hairpin structures (pre-miRNA). - Play a role in regulating gene expression.
57
siRNAs
- Produced from double-stranded RNA (e.g., viral RNA), acting similarly to miRNAs. - Involved in gene silencing through RNA degradation or translation inhibition.
58
Target Mechanism
- miRNAs/siRNAs bind to complementary 7-bp sequences in the 3’-UTR of target mRNAs. - Perfect match → destruction of mRNA, mismatch → translation attenuation.
59
RISC Complex
a multiprotein complex that regulates gene expression by silencing RNA
60
miRNA Processing
1. Pri-miRNA: Long primary transcript. 2. Pre-miRNA: Short hairpin structure. 3. RISC Complex Loading: One or both strands of pre-miRNA are incorporated into RISC.
61
miRNA Targeting in Humans
- Over 1600 miRNA genes in humans. - miRNAs can target hundreds of genes. - ~60% of protein-coding genes targeted by at least one miRNA.
62
Post-Translational Modifications (PTMs)
- Modifications made to proteins after translation to regulate function, stability, and interactions. - Common in eukaryotes, rare in prokaryotes.
63
Proteolysis (Cleavage)
- N-terminal Methionine Removal: Over 60% of proteins lose the first amino acid (methionine). - Some proteins are polyproteins that get cleaved into smaller proteins.
64
Zymogens
- Inactive enzymes that require cleavage to become active. - Examples: digestive enzymes, lysosomal enzymes.
65
Phosphorylation
- Addition of phosphate group to serine, threonine, or tyrosine. - Regulates protein activity (on/off switch). - Kinase adds phosphate, phosphatase removes it.
66
Glycosylation
- Addition of sugar groups (carbohydrates) to proteins. - Affects protein folding, stability, and signaling.
67
Ubiquitination
- Addition of ubiquitin to proteins, signaling their degradation. - Targets proteins for degradation via the proteasome.
67
Lipidation
- Addition of lipid groups (e.g., fatty acids) to proteins. - Mediates membrane anchoring and signal transduction.
68
Polypeptide becomes
Protein, once it has been folded into its shape
69
Kinase
an enzyme that adds phosphates
70
Phosphates
act as an on and off for proteins

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