THEME 3 MOD 3 Flashcards
(18 cards)
how do cells differntiate?
gene regulation and expression from environmental and cellular cues differentiates structures and therefore function by binding proteins around their promoter
gene regulation results in different/altered proteomes contributing to cellular differentiation
how many cell types to developed adults have
200
examples of cell types
RBC, muscle cells, hepatocytes, neurons, epithelial cells
differentiation during early developmental cascade contributes to specialized cells in adults
Why are transcription factors important?
proteins that bind to specific dna sequences
their structure can interact nicely with the dna double helix and control transcription
help differentiate cells
what contributes to specialized cells
gene expression patterns triggered in stem cells during development
extracellular cues
how proteins determine cell types
some proteins only exisit in specific cells or their concentrations vary
similarities in transcriptional regulation between prokaryotes and eukaryotes
proteins can activate and repress transcription
rna polymerase binds to promoter upstream of gene of interest to intiate trancsription
what makes eukaryotic transcription unique?
organized differently
prokaryotic genome has default βonβ of transcription
each gene controlled by own promoters and enhancers
dna organized into high packed chromatin (cannot be transcribed unless unwound
eukaryotic dna organization
dna tightly wound around histone proteins forming nucleosomes
histone tails are positively charged and interact well with negative phosphates in dna
each nucleosome is an octamer of 8 histone proteins 150 dna base pairs wrap around
how can chromatin be unwound for transcription?
chromatin remodelling
activator proteins recruit coactivator enzyme histone acetyltransferase (HAT) which attaches acetyl gorups to the lysine aas along histone protein tails. this lowers positive charge of histone tails loosening/unwinding the heterochromatin (condensed dna)
how alterations to histone protein tails affect charge (alterations of amino acid sequences protruding for histone tails)
degree of mods determined by histone code can activate or inhibit transcription
activates transcription:
- methylation (single methyl group added) of lysine and arginine
- acetylation of lysine
inhibits: methylation with 3 methyl groups
phosphorylation of serine of threonine can also occur
how do transcription factors work?
structural and chemical complimentary between dna and proteins allows them to bind to specific nucleic acid sequences
consume conformation that controls transcription
alpha helical domains that fit nicely in major grooves of dna, hydrogen bonds occur between amino acids of protein and nitrogenous base functional groups of dna
classified by binding motifs: helix loop helix, helix turn helix, zinc finger, leucine zipper regions
may recruit other transcription factors, rna polymerase
promoter region and core promoter
cis-sequences of dna
recruits and binds rna polymerase to intiate transcription
consists of TATA box and BRE region close to transcriptional start sites
TATA box region recognized by TATA binding protein (TBP) subunit of TFIID transcription factor
BRE (b recognition element) region recognised and bound by TIIFB general transcription factor
how do enhancer regions work?
encompasses regulatory promoter regions where specific transcription factors bind and interact with basal machinery / rna polymerase at promoter to enhance transcription and cause looping of dna
enhancer regions may be further from \promoter regions in eukaryotes
what do adaptor/mediator proteins do
connect proteins at enhancer to core promoter region for transcription to begin
what are silencer regions how do they work?
upstream of gene, activated by repressor protein which inhibits assembly of general transcription factor, mediator proteins, and cause rna polymerase to not be able to bind
hemoglobin significance in gene regulation
blood cell progenitors (stem cells preceding RBCs in adults) express different hemaglobin proteins than RBCs in adults
in fetus: two alpha globin proteins, two gamma globin (binds to oxygen more strongly, since fetus has lower oxygen supply) in the tetrameric hemoglobin
- chromatin wound up aroun beta globlin gene
in adult: two alpha globin, two beta globon in tetrameric hemoglobin
- switch from gamma to beta globin proteins facilitated by transcription factors that silence gamma globin gene transcription and others that activate beta globin gene transcription
methylation (epigenic mechanism)
cytosine within CpG islands near promoter can be methylated, changing the shape of the promoter region, inhibiting transcription
histone deacetylases can bind to methylated region and remove acetyl groups from surrounding histones, causing nucleosomes to reassemble, masking enhancer and promoter sequences