Part II-E Regulation Expression Eukaryotes (Exam 2)

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Questions and Answers

Which process is responsible for regulating transcriptional activity through structural organization of DNA?

Post-transcriptional regulation

Regulation via non-coding RNAs

Genome/chromatin structure (correct)

Transcriptional regulation

What is the significance of DNA methylation in gene expression?

Recruits chromatin remodeling complexes

Enhances transcription factor binding

Associated with transcriptional repression (correct)

Increases chromatin accessibility

What type of RNA is involved in the regulation of gene expression by influencing chromatin structure?

rRNA

ncRNA (correct)

mRNA

tRNA

During which stage of development does X-inactivation occur?

Embryogenesis Signup and view all the answers

What is the role of chromatin binding proteins in gene regulation?

They recognize epigenetic marks to establish chromatin states. Signup and view all the answers

What is the primary function of epigenetic memory during cell division?

To ensure epigenetic marks are inherited through mitosis Signup and view all the answers

Which type of chromatin is primarily associated with active transcription?

Euchromatin Signup and view all the answers

What phenomenon describes the differential expression of genes depending on whether they are inherited from the mother or father?

Imprinting Signup and view all the answers

What is indicated by the presence of 15% of genes outside the PAR in Xi?

Xi contains active genes. Signup and view all the answers

Which statement accurately reflects the role of enhancers in gene expression?

Enhancers facilitate DNA looping for gene interaction. Signup and view all the answers

What occurs during transcription elongation when TFIIH binds the promoter?

Transcription does not proceed without p-TEFb phosphorylation. Signup and view all the answers

How does Waddington's epigenetic landscape describe the increase in epigenetic restriction?

It correlates enhanced cellular differentiation with increased restriction. Signup and view all the answers

What is a significant consequence of the transcription of non-coding RNAs (ncRNAs)?

They may silence transposons and interfere with sense transcription. Signup and view all the answers

What is the primary purpose of chromatin remodeling complexes at promoters?

To ensure nucleosome-free regions for pre-initiation complex assembly. Signup and view all the answers

What role do alternate promoters play in gene expression?

They allow for diverse expression patterns from a single gene. Signup and view all the answers

Which factor is essential for the termination of transcription by RNA polymerase II?

Polyadenylation signals are critical for PAS activation. Signup and view all the answers

What is the primary role of the antisense transcript produced by LUC7L in relation to the HBA1 gene?

To methylate the HBA1 promoter Signup and view all the answers

What effect does the antisense transcript ANRIL have on the CDKN2B–CDKN2A locus?

It induces long-term DNA methylation Signup and view all the answers

What is a common feature of RNA-binding regulatory proteins in relation to mRNA?

They can impact ribosome advancements through stem-loop structures Signup and view all the answers

How do iron regulatory proteins regulate mRNA translation in iron-depleted cells?

By binding to IREs in the 5’ UTR to repress translation Signup and view all the answers

What is the function of HOX transcript antisense RNA (HOTAIR)?

To recruit PRC2 to silence the HOXD locus Signup and view all the answers

What process is influenced by alternative splicing in gene expression?

It alters post-translational modifications of proteins Signup and view all the answers

In the context of ncRNAs, what role do miRNAs play?

They can repress target mRNAs through 3’ UTR binding Signup and view all the answers

What is a potential impact of epigenetic marks on splicing?

They modulate RNA polymerase activity impacting splicing Signup and view all the answers

Which protein is involved in regulating hair growth and functions as a transcriptional corepressor?

TPO gene protein Signup and view all the answers

What condition is caused by mutations in the upstream ORF of the gene associated with hair growth?

Marie Unna hereditary hypotrichosis Signup and view all the answers

Which type of RNA is involved in the silencing of rDNA loci?

pRNA Signup and view all the answers

Which complex does PAPAS associate with to promote transcriptional repression of rDNA?

Chromatin remodeling complex CHD4/NuRD Signup and view all the answers

What do mutations in the gene associated with hair growth potentially cause other than hereditary hypotrichosis?

Congenital alopecia Signup and view all the answers

Which process is primarily regulated by the gene encoding the protein involved in hair growth?

Gene transcription Signup and view all the answers

Which of the following statements is true about the TPO gene?

It interacts with multiple nuclear receptors. Signup and view all the answers

Which of the following best describes the role of RNAPII in the context of rDNA?

It mediates antisense transcription of rDNA. Signup and view all the answers

Study Notes

Resilience

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PART II-E: Control of Gene Expression (Eukaryotes)

Gene regulation in eukaryotes occurs at multiple levels, impacting various stages.

Regulation of Gene Expression

Regulation occurs at these levels:
- Genome/chromatin structure
- Epigenetic profile and imprinting
- Transcriptional regulation
- Post-transcriptional regulation
- Regulation of Translation
- Regulation via non-coding RNAs (ncRNAs).

Genome and Chromatin Structure

Euchromatin and heterochromatin:
- Transcription occurs in euchromatic DNA.
- CTCF defines boundaries between euchromatic and heterochromatic regions.
Chromosome territories:
- Regions closer to the nuclear envelope are often silenced.
- TADs (Topologically Associating Domains):
  - Different cell types have unique active/inactive TAD profiles.
ncRNAs (non-coding RNAs):
- Bind DNA and proteins involved in DNA/RNA binding.
- Located in scaffolding complexes affecting chromatin structure.
- Can recruit chromatin remodeling complexes.

Epigenetic Profile and Imprinting

Epigenetic mechanisms:
- Histone modifications
- Nucleosome positioning
- DNA methylation
Chromatin structure is closely linked to the epigenetic profile.
Epigenetic code:
- Chemical modifications on histones create chromatin states with varying transcription levels.
- Chromatin-binding proteins recognize epigenetic marks to establish open/closed chromatin.

DNA Methylation (5-meC of CpG)

Associated with transcriptional repression.
Transcription factors cannot bind methylated DNA.
Specific proteins bind methylated DNA for chromatin organization and epigenetic maintenance.
Epigenetic memory is maintained through mitosis.
CpG islands in gene-rich regions are typically unmethylated.
During gametogenesis, the epigenome resets to a totipotent state.
Imprinting:
- Approximately 150 human genes are imprinted.
- Differential expression from maternal/paternal chromosomes.
- Methylation of maternal DMR is a common mechanism for imprinting.

Transcriptional Regulation

Nucleosome positioning:
- Promoters lack nucleosomes during transcription initiation complex (PIC) assembly.
- Chromatin remodeling complexes are involved.
Promoters:
- About half of mammalian genes have alternative promoters.
Enhancers:
- Involved in cell- and tissue-specific gene expression.
- DNA interactions (cohesin, mediator proteins) are crucial.
- TAD structure facilitates interactions.

Transcription Factors and the Epigenetic Landscape

A variety of general and tissue-specific transcription factors govern development and expression.
Cell differentiation is accompanied by increasing epigenetic restriction.

Regulation of Translation

Leader peptides:
- About a third of human transcripts include upstream open reading frames (uORFs).
mRNA structure:
- Stem-loop structures affect ribosome movement.
- RNA-binding proteins bind to mRNA.
ncRNAs (non-coding RNAs):
- miRNAs, siRNAs, and piRNAs can repress target mRNA expression.
- miRNAs bind to 3' untranslated regions (UTRs) to modulate translation rates.
- miRNAs can compete for target mRNAs (regulating networks of moderate effects).

Additional topics

X-inactivation is an epigenetic process in early embryogenesis, balancing the expression of X-linked genes. There is random X inactivation in the blastula.
XIC: X inactivation center (1 Mb)
19 Kb ncRNA: (X inactivation specific transcript) is abundant in the chromosome slated to be inactivated.
Y chromosome (Protein-coding genes): contains approximately 45 protein-coding genes, whereas the X chromosome has 1,000-2,000 protein-coding genes.
Post-transcriptional regulation:
- Alternative splicing is regulated by splicing enhancers/suppressors, producing strong or weak splice sites based on tissue type.
- Impacts include sub-cellular compartment signals, transmembrane domains, and modification of proteins.
- RNA turnover and RNA editing processes.

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