6.6 Gene Expression and Cell Specialization

Eukaryotic Gene Regulation

gene regulation in eukaryotes can occur at several different stages:

chromatin remodeling

transcription (most genes regulated at this level)

RNA processing

RNA stability

Translation

Post-translation

Chromatin Remodeling

if DNA is tightly wound it is less accessible for transcription

how can it be modified?

histone acetylation loosens (accessible)

DNA methylation condenses (inaccessible)

epigenetic inheritance

Histone Acetylation

adds acetyl groups to histones, which loosens the DNA (accessible)

DNA Methylation

adds methyl groups to DNA, which causes the chromatin to condense (inaccessible)

Epigenetic Inheritance

inheritance that involves changes in how a gene is expressed without any changes in that gene’s nucleotide sequence (ex. methylation)

can be passed on during cell division

modifications can be reversed, unlike mutations

explains why one identical twin may express a disease while the other does not

Transcription

once chromatin modifications allow the DNA to be more accessible, specific transcription factors can bind to control elements

groups of genes with related functions may be regulated together if they share common control elements recognized by the same transcription factors (even if located on different chromosomes), which allows for coordinated regulation of related processes

Control Elements

sections of noncoding DNA that can be located near (proximal) or far (distal) from the promoter

includes enhancers

the rate of gene expression can be regulated by binding of transcription factors

groups of genes with related functions may be regulated together if they share common control elements recognized by the same transcription factors (even if located on different chromosomes)

this allows for coordinated regulation of related processes

Enhancers

distal control elements can be grouped together as enhancers

can be either upstream or downstream of the transcription start site

Activators

can bind to enhancers to increase the rate of transcription

even though enhancers are located far from the promoter, DNA is flexible and can bend

DNA’s flexibility and bending allows activators to interact with mediator proteins, which recruit general transcription factors and RNA polymerase to begin transcription

RNA Processing

adding poly-A tail and 5’ cap

alternative splicing of pre-mRNA

RNA Stability and Transport

RNA transport: controlling access to nuclear pores regulates mRNA transport to cytosol

RNA stability: lifespan of mRNA in cytosol affects how many protein molecules can be translated from it

microRNAs and small interfering RNAs can bind to mRNA and degrade it or block translation

Translation

the initiation of translation can be blocked by regulatory proteins that bind to sequences in the 5’ cap or poly-A tail, which prevent the ribosome from binding

modification (activation/inactivation) of proteins that help ribosomes attach to mRNA

Post-Translation

protein modifications

ex. addition/removal of phosphate groups for activation/inactivation or chemical tags for degradation