Lecture 17: Gene Expression Flashcards
• Understand the concepts of nucleosomes and chromatin structure • Understand that chromatin remodeling complexes, histone modification enzymes, and DNA methylation can all regulate chromatin structure, thus affecting gene expression • Understand the concept of a “master regulator” • Understand that cell memory can be mediated by positive feedback, DNA methylation or histone modification • Understand the concept of epigenetic inheritance
transcriptional regulators are…
activators or repressors
have DNA sequence specificity
act alone or together
diff types of chromatin: constitutive heterochromatin, facultative chromatin, euchromatin
constitutive heterochromatin: TM cannot enter, repressive, transcriptionally silent, very tightly packed, contains telomeres (ends) and centromeres (middles)
facultative heterochromatin: contains genes and varies its location in diff. cell types
euchromatin: not as tightly packed, rich in genes, allows transcription to proceed
*nucleosomes can restrict access of TM to DNA
interphase: transcription ON
mitosis: transcription OFF
function of the tight packing of chromatin
tight packing inhibits transcription
therefore genes can be turned on and off by factors that influence chromatin packing
factors such as:
- chromatin remodeling complexes
- histone modifying enzymes
- DNA methylation
chromatin remodeling complexes
Chromatin remodeling complexes
use the energy of ATP to loosen
the nucleosomal DNA and push it
along the histone octamer
DNA more accessible to
other proteins which
facilitates transcription
histone modifying enzymes
ways to modify core histone tails - each has a specific effect on chromatin packing:
Methylation - represses arginines/lysines
Acetylation - activates, opens up lysines
Phosphorylation - serine
nomenclature examples:
H3K9me = histone H3 methylated on lysine (K) position 9
H3k27ac = histone H3 acetylated on lysine (K) located in position 27
histone modification can affect chromatin structure by:
- directly by altering the affinity of tails for
adjacent nucleosome - indirectly by attracting general
transcription regulators and chromatin
remodeling complexes (H3K9)
Histone modification is reversible
* some enzymes add these modifications
* other enzymes remove these modifications
transcriptional regulators can alter chromatin
tightly packed histone octamer can be unwinded via chromatin-remodeling complexes, makes TATA box more accessible
it can also be altered by histone acetyltransferase (transcriptional activator), performs specific pattern of histone acetylation
Transcriptional regulators:
-activators -> turn transcription ‘ON’
-repressors -> turn transcription ‘OFF’
DNA methylation
act as repressers
methyl group always added to cytosine of a CpG island
unmethylated CpG islands:
recruit proteins that decondense chromatin & activate gene expression
methylated CpG islands:
recruit proteins that condense chromatin & repress gene expression
what does this image convey
conveys how you can utilize 3 transcriptional regulators to generate 8 diff. cell types
is this asymmetric cell division?
transcriptional regulators can assemble into different complexes to regulate the expression of different genes
chronic stress will downregulate immune system
unqiue transcriptional factors work on different genes for the same signal
example of a transcription factor which can lead to the formation of an entire organ (master regulator)
MRs are both necessary and sufficient for organ formation
Necessary: loss of eyeless gene (eyeless mutation) results in the loss of eye
Sufficient: ectopic expression of eyeless resultls in the formation of ectopic eye (eye in the leg)
