Overview: Eukaryotic gene regulation
- Gene regulation is the process of controlling which genes in a cell's DNA are expressed (used to make a functional product such as a protein).
- Different cells in a multicellular organism may express very different sets of genes, even though they contain the same DNA.
- The set of genes expressed in a cell determines the set of proteins and functional RNAs it contains, giving it its unique properties.
- In eukaryotes like humans, gene expression involves many steps, and gene regulation can occur at any of these steps. However, many genes are regulated primarily at the level of transcription.
Gene regulation makes cells different
How do cells "decide" which genes to turn on?
- Examples of information from inside the cell: the proteins it inherited from its mother cell, whether its DNA is damaged, and how much ATP it has.
- Examples of information from outside the cell: chemical signals from other cells, mechanical signals from the extracellular matrix, and nutrient levels.
- The cell detects the growth factor through physical binding of the growth factor to a receptor protein on the cell surface.
- Binding of the growth factor causes the receptor to change shape, triggering a series of chemical events in the cell that activate proteins called transcription factors.
- The transcription factors bind to certain sequences of DNA in the nucleus and cause transcription of cell division-related genes.
- The products of these genes are various types of proteins that make the cell divide (drive cell growth and/or push the cell forward in the cell cycle).
Eukaryotic gene expression can be regulated at many stages
- Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. More open or “relaxed” chromatin makes a gene more available for transcription.
- Transcription. Transcription is a key regulatory point for many genes. Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA.
- RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA molecule can be regulated, and so can exit from the nucleus. Different mRNAs may be made from the same pre-mRNA by alternative splicing.
- Chromatin structure. Chromatin may be tightly compacted or loose and open.
- Transcription. An available gene (with sufficiently open chromatin) is transcribed to make a primary transcript.
- Processing and export. The primary transcript is processed (spliced, capped, given a poly-A tail) and shipped out of the nucleus.
- mRNA stability. In the cytosol, the mRNA may be stable for long periods of time or may be quickly degraded (broken down).
- Translation. The mRNA may be translated more or less readily/frequently by ribosomes to make a polypeptide.
- Protein processing. The polypeptide may undergo various types of processing, including proteolytic cleavage (snipping off of amino acids) and addition of chemical modifications, such as phosphate groups.
- RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be chopped up.
- Translation. Translation of an mRNA may be increased or inhibited by regulators. For instance, miRNAs sometimes block translation of their target mRNAs (rather than causing them to be chopped up).
- Protein activity. Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups. These modifications can be regulated and may affect the activity or behavior of the protein.