Promoters & Suppressors (College Board AP Biology)

Promoter Sequences

• Only some DNA sequences code for the production of polypeptides, these are called coding sequences
• Noncoding sequences produce functional RNA molecules like transfer RNA (tRNA) or are involved in the regulation of gene expression such as enhancers or promoters
  • The promoter is a noncoding sequence located near a gene whereas enhancers are noncoding regions of DNA that are usually found further away from a gene
  • The promoter and enhancer regions are not transcribed
• Transcription factors are a type of protein molecule that bind to the promoter or enhancer sequences to help initiate transcription
  • This helps RNA polymerase to attach to the promoter and result in an increase in the rate of transcription
  • These transcription factors regulate transcription and ensure that only the required genes are expressed in the correct cells, at the correct time and to the appropriate level depending on the specific needs of the cell
  • This is the most common way for cells to control gene expression

A Promoter Region and the Bonding of a Transcription Factor Diagram

A transcription factor binding to the promoter region of a gene which allows RNA polymerase to bind and for transcription to occur

Suppressor Sequences

• Some factors inhibit gene expression by binding to DNA and blocking transcription
• These are called suppressors
• The most widely documented are tumor-suppressor genes
• These code for proteins that help keep cell division under control

Tumor suppressor genes

• Cancers demonstrate how important it is that cell division is precisely controlled, as cancers arise due to uncontrolled mitosis
  • Cancerous cells divide repeatedly and uncontrollably, forming a tumor (an irregular mass of cells)
• Tumor suppressor genes are normal genes that code for proteins that regulate the cell cycle
• The proteins encoded for by tumor suppressor genes carry out the following functions:
  
  • DNA repair
  • Slowing the cell cycle by ensuring checks are made
  • Signalling apoptosis (cell death) when the cell is faulty
• These proteins ensure that cells do not replicate if they contain mutated DNA or are faulty as these characteristics can lead to tumor formation
• Tumors develop if tumor suppressor genes are mutated or silenced
  • A mutation can be any type that results in a non-functional protein
  • Silencing can occur through epigenetic changes
    • Hypermethylation of DNA (over-addition of methyl groups to cytosine nucleotides) causes transcription inhibiting proteins to bind the DNA
      • If this occurs around tumor suppressor genes, this could result in tumor development as the necessary regulatory proteins coded for by tumor suppressor genes will not be produced

• Gene regulation mechanisms such as promotors, suppressors, transcription factors, and epigenetics (amongst others), all play a role in differential gene expression
• Stem cells become specialized through differential gene expression
  
  • This means that only certain genes in the DNA of the stem cell are activated and get expressed
• Every nucleus within the stem cells of a multicellular organism contains the same genes, that is, all stem cells within an organism have an identical genome
• Despite the stem cells having the same genome, they are able to specialize into a diverse range of cell types because during differentiation certain genes are expressed ('switched' on)
• Controlling gene expression is the key to development as stem cells differentiate due to the different genes being expressed
• This differentiation occurs via the following basic steps:
  • Under certain conditions, some genes in a stem cell are activated, whilst others are inactivated
  • mRNA is transcribed from active genes only
  • This mRNA is then translated to form proteins
  • These proteins are responsible for modifying the cell (e.g. they help to determine the structure of the cell and the processes that occur within the cell)
  • As these proteins continue to modify the cell, the cell becomes increasingly specialized
  • The process of specialisation is irreversible (once differentiation has occurred, the cell remains in its specialised form)

Differential Gene Expression Diagram

Differential gene expression results in the differentiation of stem cells

Role of RNA in Regulating Gene Expression

• In addition to the main types of RNA (mRNA, tRNA and rRNA), certain other small RNA molecules play a role in regulation of gene expression

Small Nuclear RNA

• Small nuclear RNAs (snRNA) are noncoding RNAs that are responsible for splicing introns
• Introns are then removed from the pre mRNA transcript and mature mRNA forms.

MicroRNA

• MicroRNAs (miRNA) are noncoding RNAs mainly involved in gene regulation. They are mostly processed from introns
• Studies have shown that miRNAs that bind to an untranslated region on mRNAs to suppress translation
• Also, miRNA binding to promoter regions can boost transcription
• miRNAs can also function similarly to hormones
  • They are released into the tissue fluid and taken up by other cells for regulation of cellular activity
  • miRNAs are ideal biomarkers for the diagnosis of various diseases including in cancer through their role in controlling oncogenes and tumor suppressors

Small Interfering RNA

• Small Interfering RNAs (siRNA) are double-stranded, noncoding RNAs that inhibit gene expression through RNA interference
  • They interfere with gene expression by degrading mRNA and preventing the translation of proteins
  • siRNAs have the potential to be therapeutic agents for diseases due to their potency and ability to destroy genes.
  • Unlike miRNAs, siRNAs can specifically target a gene of choice