Chapter 13
11/17/04
Activation Domains
Physically interact with general TFs or other proteins.
These interactions facilitate assembly of Pol II Initiation Complex on promoter &
initiation of txn.
Summary:
In order to initiate txn, RNA Pol II Initiation Complex must assemble on the promoter.
TFIID binding to TATA box within core promoter directs where Initiation Complex will
form and in which direction txn will proceed.
However, Initiation Complex needs the help of other proteins, Activators, in order to
assemble.
Some Activators bind to promoter-proximal elements, others bind to enhancer elements,
due to the sequence-specific DNA binding properties of their DNA binding domains.
Activators' activation domains physically interact with general TFs to facilitate assembly
of Initiation Complex.
Tissue-specific &/or temporal regulation of txn of genes is controlled by when Activators
are expressed &/or they are able to bind to a gene's enhancer element(s).
Some genes have multiple enhancer elements that regulate txn in different tissues or at
different times.
These contain binding sites for different Activators that may be present at different times
or in different tissues.
Epigenetic gene regulation:
Heritable modifications to gene expression that don’t involve changes to DNA sequence.
Heritable alterations in gene expression may involve:
DNA methylation (specifically, C’s of CG doublets)
Changes in chromatin structure
Accessibility of TFs to target sites &/or ability to activate txn can be controlled by
the level of compaction of chromatin fibers.
This often involves covalent modification of histones, such as acetylation or
methylation of lysine residues.
X-inactivation in female mammals:
In order to have equal expression of X-linked genes in female and male cells, one of two
X chromosomes in female mammal cells becomes inactivated during early
embryogenesis.
Initially, X-linked Xist gene is expressed at low levels from both maternal and paternal X
chromosomes.
Then, Xist gene from one X (either maternal or paternal, randomly selectced in each cell)
is transcribed at higher level and coats X in cis.
This leads to chromatin condensation and DNA methylation.
This X is then permanently heterochromatic, preventing expression of its genes.
Example of this phenomenon: Calico cats.
Parental imprinting:
Expression of alleles of some autosomal genes is determined by which parent they’re
inherited from.
A few (rare) genes are differently methylated during oogenesis vs spermatogenesis.
Example:
Prader-Willi Syndrome (PWS)
PWS gene is methylated during oogenesis. Therefore, can only express
paternally inherited PWS allele.
Summary:
Txn of genes is regulated by binding of TFs to enhancers/silencers.
Chromatin structure can modulate ability of activators to bind to DNA &/or activate txn.