T3M3 Flashcards
All embryonic stem cells are…
identical
How many distinct cell types in adult human?
200
Transcription factors are
proteins that bind to specific DNA sequences
Controlling which gene is active along the chromosome leads to
vast array of cell types found throughout our bodies
Both prokaryotes and eukaryotes have
proteins that are involved with activating and repressing transcription and utilize RNA polymerase to bind to promoters that are upstream of genes to initiate transcription
In the prokaryotic genome
groups of related genes with similar functions can often be found clustered together into operons transcribed by a single promoter
eukaryotic genome
each gene is controlled by its own promoters
and enhancers
DNA in eukaryotes is organized into
highly compacted chromatin
DNA in tightly wound chromatin fibers makes for
- fit all the DNA within the nucleus
- DNA to be moved around during cell division
Winding of DNA in nucleosomes can affect
whether DNA is transcribed or not
Genes within this tightly wound heterochromatin are usually
not expressed
To be able to transcribe a specific gene product
Must unwind DNA
DNA compaction regulates
gene expression
In eukaryotes DNA is
around a complex of histone proteins, forming the nucleosome structure
Each nucleosome contains
an octamer of 8 histone proteins around which approximately 150 DNA base pairs wrap around
When DNA is tightly wound into chromatin
the DNA is not accessible due to the tight winding around the histone proteins
For transcription to occur chromatin must be
unravelled
chromatin unravelled through
chromatin remodelling
chromatin remodeling begins when
an activator protein or transcription factor is
able to bind to an accessible enhancer site. This
leads to the further recruitment of other proteins that can lead to further chromatin remodeling
Transcription requires changes to chromatin structure to enable
transcription factors to bind important DNA regions, recruit RNA polymerase, and facilitate the transcriptional process
DNA is tightly wound around histone proteins due to
the interactions of the positively charged tails of histone proteins with the negatively charged phosphates in DNA
During the chromatin remodeling process, activator proteins can
recruit the coactivator enzyme histone
acetyltransferase (or HAT)
HAT can
attach acetyl groups to lysine amino acids along the positively charged tails of nucleosome histone proteins
When tails are acetylated
positive charge is reduced, and the interaction between the histones and the wound DNA is weakened
other chemical modifications
methylation of lysine and arginine and phosphorylation of serine and threonine amino acids along the histone protein tails
Acetylation and methylation with a single
methyl group allows for
transcriptional activation
Methylation with 3 methyl groups leads to
repression of transcription
Most transcription factors can be classified based on
structures of their distinct DNA binding motifs
DNA binding motifs include
the basic helix-loop-helix, helix-turn- helix, zinc finger and leucine zipper regions
To initiate transcription in eukaryotes
specific DNA sequences (or cis-sequences) are required
The TATA box and transcriptional start sites form
part of the core promoter
The core promoter is
the binding site that is required for binding of RNA polymerase and associated transcription factors
The TATA box and BRE regions are generally situated
in close proximity to the transcription start site
The enhancer regions are able to
bind cell or region-specific transcription factors
Flexible nature of DNA allows for
assembled transcription factors and RNA
polymerase to come to close proximity by looping of the DNA
Adaptor or mediator proteins are
able to
connect the proteins that are bound to the
enhancer regions with proteins that are bound to the core promoter region
When the silencer regions of the DNA
are activated by a repressor protein
interference of the general transcription factor
assembly and mediator activity which is needed for the binding of RNA polymerase and subsequent transcription
Blood cell progenitors (or stem cells)
differentiate into
functional red blood cells that contain haemoglobin
Progenitor cell must
activate transcription of globin proteins that are
appropriate for the fetus or the adul
Fetus globin proteins
2 alpha-globin proteins making up half of their tetrameric hemoglobin protein, 2 gamma-globin proteins
Adult globin proteins
2 alpha-globin proteins making up half of their tetrameric hemoglobin protein, beta-globin proteins making up the other half of the hemoglobin protein
Gamma globin can bind
oxygen more strongly than beta globin
In the fetal blood cell progenitors
chromatin is wound up around the beta-globin gene to inhibit transcription, while the chromatin around the gamma-globin gene
is open to allow transcription
In adult cells chromatin
reorganized to prevent transcription of the gamma-globin gene but allow transcription of the adult beta-globin gene
histone modifications permit
Unwinding of DNA from the nucleosomes to allow DNA-binding transcription factors to associate with enhancer and promoter sequences on the DNA and start transcription
DNA modifications, such as methylation
of certain nucleotides, can still
inhibit transcription
In eukaryotic systems, transcription is affected by
the chemical modification of cytosine bases in the DNA sequence
Most common cytosine base modification is
addition of a methyl group
addition of a methyl group occurs
within a string of cytosine and guanine bases called a “CpG” island
When a CpG island contains many methylated cytosine bases
the shape of the DNA binding site for the proteins has changed and the proteins can no longer bind
Heavily methylated promoters
are not transcriptionally active because the RNA polymerase cannot bind to the methylated sequences
DNA methylation is an example of
epigenetic mechanism that controls
gene expression
