Eukaryotic gene regulation Flashcards
how is transcription initiated
transcription factors and RNA polymerase bind to promoter region upstream from a gene
chromosome puff
visible expanded region on a chromosome where active transcription occurs
heterochromatin
densely packed
genes silenced
euchromatin
loosely packed
chromatin remodelling complexes
reposition nucleosomes allowing
transcription factors and RNA
polymerase to bind to promoters
and initiate transcription.
Uses energy from ATP
histone modification concepts
Chromatin contains +ve lysine
and arginine amino acid
residues that electrostatically bind to negatively charged phosphate group on dna backbone
acetylation of amino acids alters charge on histone proteins to alter ability to bind to dna
acetyltransferases, deacteylases, methyltransferases etc
histone acetyltransferases
add acetyl groups (from acetyl-CoA) to the lysine residues on histone proteins, neutralising the positive charge that attracts the DNA to the nucleosome
histone deacetylases
remove acetyl groups
restore charge
blocks transcription
effects of histone acetyltransferases on transcription
structural changes to chromatin, leading to chromatin relaxation. Heterochromatin to
Euchromatin. Recognition site for
transcriptional activator-more open
DNA methylation
addition of methyl groups to cytosines
5-methylcytosine
recruits histone-modifying proteins to stabilise the chromatin
heritable
blocks TFs
CpG islands
clusters of adjacent CG nucleotides near promoter
genomic imprinting
form of gene expression where only one allele, either maternal or paternal, is expressed (other is silenced)
imprinted genes are passed down
regulated by epigenetuc modifications
genomic imprinting with pregnancy
IGF2 and H19
IGF2 paternally expressed and promotes fetal growth
H19 maternally expressed, limits excessive growth/removal of resources from mother
mechanism of x chromosome inactivation
Xist RNA binds to XIC (X chromosome inactivation centre). Xist RNA coats chromosome which triggers methylation and modifications that reduce transcription
Prevents overexpression of genes in females
Xist gene
codes for RNA that is transcribed and undergoes splicing but does not code for a protein
recruits factors promoting methylation of DNA and histone modification
core promoter
specific DNA sequence that RNA
polymerase and transcription
factors recognise
Contains TATA box
regulatory promoter
upstream from core promoter
TF binding site
forms transcription initiation complex
basal transcription apparatus
TATA
general TFs
RNA polymerase
transcription factors (structure)
contain one or more DNA binding motifs that bind to DNA
TFs in prokaryotes and eukaryotes
helix-turn-helix
alpha helices fit into major groove of DNA
TFs in eukaryotes only
zinc fingers
leucine zipper (main)
specific transcription factors
can act as activators or repressors, either directly, or by binding cofactors
enhancers
bind to activators (TFs)
can undergo DNA looping to get close to gene
silencers
bind to repressors
transcriptional synergy
multiple TF work together to increase level of gene expression, interact cooperatively
Number of enhancer sequences affects amount of transcription
insulators
blocks activity of an enhancer on a promoter
only when it lies between the two
help create regulatory neighbourhoods
regulatory neighbourhoods
Chromatin loops where genes and their regulatory elements interact more frequently
topologically associating domains
Held together by CTCF protein that helps form the loops by binding insulators
cohesin also involved
Maintains genome structure and prevents unwanted interactions between genes
TAD
enhancers can interact with promoters only in the same TAD
pre-initiation complex
Large protein complex of RNA polymerase II, general TFs and coactivators
General transcription factors and RNA polymerase assemble on core promoter
assembly of pre initiation complex
TFIID (TF) binds to TATA box
other TFs recruited
RNA polymerase II recruited
initiation of RNA synthesis
RNA polymerase II is phosphorylated by TFIIH, initiating transcription process
RNA polymerase moves along strand
TFIIH unwinds double helix
