Regulation of Genetic Expression

• to be expressed, each gene requires a particular set of transcription factors

• different cells have different sets of specific transcription factors

  • ex. an anabelps has eye cells specialized for aerial vision and eye cells specialized for aquatic vision

How can two cells with the same set of genes function differently?

gene regulation

encompasses the ways in which cells control gene expression

• where (in which cells) are turned on?

• when (during development or in response to changes in the environment) are genes turned on?

• how much gene product is made?

• chromatin modification

• histone tail modification

• DNA methylation

• epigenetic inheritance

What are some things that happen pre-transcription?

the proteins that carry out transcription cannot access the DNA

What happens when chromatin is coiled?

chromatin

a complex of DNA, RNA, and proteins that gives chromosomes their structure; the way that eukaryotic DNA is packaged

to allow space for transcriptional enzymes and proteins to work

Why must chromatin unravel?

chromatin remodeling

the nucleosomes are repositioned to expose different stretches of DNA

• acetyl groups are attached to an amino acid in a histone tail

• reduces affinity of DNA to histone

  • acetyl groups negatively charged

  • reduces positive charge of histone → makes promoter region available

• appears to open up the chromatin structure, thereby promoting the initiation of transcription

What is histone acetylation?

• the addition of methyl groups to certain bases in DNA is associated with reduced transcription

• the most common chemical modification to DNA is the addition of a methyl group to the base cytosine

• can cause long-term inactivation of genes in cellular differentiation

What is DNA methylation?

• the inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence

• might explain cases where one identical twin develops a genetically based disease, while the other does not

What is epigenetic inheritance?

• modification of cytosine bases

• changes to histones

• altering chromatin structure

What are some epigenetic effects?

• nucelosomes can slide along DNA

• when nucleosomes are spaved closely together, transcription factors can’t bind

• when nucleosomes are spaced apart DNA is exposed → transcription factors can bind

What are some main points of methylation?

• regulation of initiation

• transcription factors

• proximal regulation

• distal regulation

• cell-specific transcription

What are some qualities of transcription?

• associated with most eukaryotic genes are multiple control elements, segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription

• control elements and the transcription factors they bind are critical to the precise regulation of gene expression in different cell types

How is transcription initiation regulated?

transcription factors

proteins tha help turn specific genes “on” or “off” by binding to nearby DNA

• activators →

• repressors → decrease transcription

What are the different types of transcription factors? What do they do?

• enhancers

• silencers

they can turn a gene on/off in specific parts of the body

What are different transcription factor binding sites? What do they do?

allow cells to perform logic operations and combine different sources of information to “decide” whether to express a gene

What do transcription factors allow cells to do?

general transcription factors

essential for the transcription of all protein-coding genes

• brought there by mediator proteins that bind to the TATA box

• recruit components of RNA polymerase complex

• specific transcription factors that bind to control elements that may be close to or farther away (distal) from the promoter

What do some genes require to bind to control elements?

enhancers

groupings of distal control elements

stimulates the transcription of a gene

What happens when activator proteins bind to enhancers?

• a sequence of protein → protein interactions that result in enhanced transcription of a given gene

• protein mediated bending of DNA brings bound activators into contact with mediator proteins

What do bound activators facilitate?

• a particular combination of control elements can activate transcription only when the appropriate activator proteins are present

• with only a dozen or so control elements, a large number of combinations is possible

  • e.g. activation of albumin gene in liver vs. Crystallin gene in lens cell

What happens during cell specific transcription?

• RNA processing

• alternative RNA processing

• translation regulation

• protein processing (posttranslational modification)

How can gene expression be affected post-transcription?

RNA processing

the modification of pre-mRNA by enzymes in the eukaryotic nucleus before the genetic messages are dispatched to the cytoplasm

• both ends of the primary transcript are altered

  • the 5’ end receives a modified nucleotide 5’ cap

  • the 3’ end gets a poly-A-tail

• certain interior sections of the molecule (introns) are cut out and the remaining parts (exons) spliced together

What happens during RNA processing?

different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns

• can significantly expand the repertoire of a eukaryotic genome

• more than 90% of the human protein-coding genes undergo alternative splicing

What is alternative RNA splicing?

• initiation → selected mRNAs can be blocked by regulatory proteins that bind to sequences or structures of the mRNA

• alternatively, the translation of all mRNAs in a cell may be regulated simultaneously

• translation initiation factors are simultaneously activated in an egg following fertilization

What are some ways that translation is regulated?

• processing, including cleavage, and chemical modifications (posttranslational modifications)

  • the addition of a phosphate group (phosphorylation)

What do polypeptides undergo after translation?