Transcription process, Lecture notes of Biology

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By Chris Paine
https://bioknowledgy.weebly.com/
7.2 Transcription and gene expression
Essential idea: Information stored as a code
in DNA is copied onto mRNA.
"The genetic code is frequently referred to as a
blueprint because it contains the instructions a cell
requires in order to sustain itself. We now know that
there is more to these instructions than simply the
sequence of letters in the nucleotide code, however.
For example, vast amounts of evidence demonstrate
that this code is the basis for the production of various
molecules, including RNA and protein ... In
transcription, a portion of the double-stranded DNA
template gives rise to a single-stranded RNA
molecule."
http://www.nature.com/scitable/topicpage/dna-transcription-426#
The image shows how DNA is used as
a template to create portable
molecules of genetic code, i.e. mRNA,
that can leave the nucleus for
translation in other regions of the cell.
https://commons.wikimedia.org/wiki/File:Simple_transcription_elongation1.svg
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By Chris Paine https://bioknowledgy.weebly.com/

7.2 Transcription and gene expression

Essential idea: Information stored as a code

in DNA is copied onto mRNA.

"The genetic code is frequently referred to as a blueprint because it contains the instructions a cell requires in order to sustain itself. We now know that there is more to these instructions than simply the sequence of letters in the nucleotide code, however. For example, vast amounts of evidence demonstrate that this code is the basis for the production of various molecules, including RNA and protein ... In transcription, a portion of the double-stranded DNA template gives rise to a single-stranded RNA molecule." http://www.nature.com/scitable/topicpage/dna-transcription-426# The image shows how DNA is used as a template to create portable molecules of genetic code, i.e. mRNA, that can leave the nucleus for translation in other regions of the cell. https://commons.wikimedia.org/wiki/File:Simple_transcription_elongation1.svg

Understandings, Applications and Skills

Statement (^) Guidance 7.2.U1 Transcription occurs in a 5’ to 3’ direction. RNA polymerase adds the 5´ end of the free RNA nucleotide to the 3´ end of the growing mRNA molecule. 7.2.U2 Nucleosomes help to regulate transcription in eukaryotes. 7.2.U3 Eukaryotic cells modify mRNA after transcription. 7.2.U4 Splicing of mRNA increases the number of different proteins an organism can produce. 7.2.U5 Gene expression is regulated by proteins that bind to specific base sequences in DNA. 7.2.U6 The environment of a cell and of an organism has an impact on gene expression. 7.2.A1 The promoter as an example of non-coding DNA with a function. 7.2.S1 Analysis of changes in the DNA methylation patterns.

The picture can't be displayed. 7.2.A1 The promoter as an example of non-coding DNA with a function. The promoter is a DNA sequence is located near a gene. It acts as the binding site for RNA polymerase.

Non-coding regions have important functions , for example promoters :

The adjacent gene is transcribed , but the promoter region is not. RNA polymerase transcribes the gene into RNA, typically mRNA. Operator is a region of DNA that can regulate transcription, typically inhibiting transcription (silencers are a type of operator) http://en.wikipedia.org/wiki/File:Lac_operon1.png Edited from: http://commons.wikimedia.org/wiki/File:Lac_Operon.svg

7.2.U5 Gene expression is regulated by proteins that bind to specific base sequences in DNA. One well known example of the regulation of gene expression by proteins is the metabolism of lactose in E. Coli bacterium. The diagram below illustrates this example. Genes involved in the metabolism (breakdown) of lactose The repressor protein is bound to the operator preventing RNA Polymerase from transcription of the genes RNA Polymerase Operator is a region of DNA that can regulate transcription, typically inhibiting transcription, such as this silencer sequence. The promoter is a DNA sequence is located near a gene. It acts as the binding site for RNA polymerase. The consequence of the inhibition of the lactose metabolism is that the concentration of undigested lactose now increases in E. Coli … Edited from: http://commons.wikimedia.org/wiki/File:Lac_Operon.svg DNA Strand

7.2.U5 Gene expression is regulated by proteins that bind to specific base sequences in DNA. DNA Sequence Binding protein Function Enhancers Activator Activator proteins bind to enhancer sequences of DNA to greatly increase the rate of transcription of a gene. Silencers Repressor Repressor proteins bind to non-coding regions of DNA to either block or reduce the transcription of a gene. Promoter RNA Polymerase A region of DNA located close to a specific gene. Once bound to the sequence RNA polymerase transcribes the gene.

Summary of common types of regulating proteins and associated sequences

found in eukaryotes.

7.2.U6 The environment of a cell and of an organism has an impact on gene expression.

The environment of an organism impacts

gene expression. For example human hair

and skin colour are impacted by the exposure to sunlight and high temperatures. Similarly pigments in the fur of Himalayan rabbits ( Oryctolagus cuniculus ) are regulated by temperature. Gene C controls fur pigmentation in Himalayan rabbits. The gene is active when environmental temperatures are between 15 and 25°C. At higher temperatures the gene is inactive. In the warm weather no pigment is produced and the fur is white In low temperatures Gene C becomes active in the rabbit's colder extremities (ears, nose, and feet) and produces a black pigment. http://www.alpinecommunitynetwork.com/wp-content/uploads/himalayan-bunny- 5 - 19 - 11 - 1_opt4.jpg http://upload.wikimedia.org/wikipedia/commons/0/06/Kr%C3%B3liki_kalifornijskie_666.jpg

Review: 7.1.U1 Nucleosomes help to supercoil the DNA.

Eukaryotic DNA supercoiling is organised

by nucleosomes

http://en.wikipedia.org/wiki/File:DNA_to_Chromatin_Formation.jpg

  • Nucleosomes both protect DNA and allow it to be packaged, this in turn allows DNA to be supercoiled.
  • Nucleosomes are formed by wrapping DNA around histone proteins n.b. Prokaryotic DNA is, like eukaryotic DNA, supercoiled, but differently: Prokaryotic DNA maybe associated with proteins, but it is not organised by histones and is therefore sometimes referred as being ‘naked’.

Review: 7.1.U1 Nucleosomes help to supercoil the DNA. http://en.wikipedia.org/wiki/File:DNA_to_Chromatin_Formation.jpg The H1 histone binds DNA in such a way to form a structure called the 30 nm fibre (solenoid) that facilitates further packing.

Structure of a simplified nucleosome

http://commons.wikimedia.org/wiki/File:Nucleosome_organization.png octamer (contains two copies of four different types of histone protein)

7.2.U2 Nucleosomes help to regulate transcription in eukaryotes. Edited from: http://www.nature.com/neuro/journal/v13/n4/images/nn0410- 405 - F1.jpg

Methylation is the addition of

methyl groups to DNA

Methylation of DNA inhibits transcription

Processes that inhibit transcription bind

the DNA more tightly to the histone

making it less accessible to transcription

factors (forming heterochromatin).

*Chromatin is a complex of DNA, protein and RNA. Tightly packed chromatin which cannot be transcribed is referred to as heterochromatin.

7.2.U2 Nucleosomes help to regulate transcription in eukaryotes. Edited from: http://www.nature.com/neuro/journal/v13/n4/images/nn0410- 405 - F1.jpg

Acetylation is the addition of Acetyl

groups to histones

n.b. Methylation of histones can also

occur, this process can both promote

and inhibit transcription.

Acetylation promotes transcription

Processes that promote transcription

bind the DNA more loosely to the

histone making it more accessible to

transcription factors (forming

euchromatin* ).

*Chromatin is a complex of DNA, protein and RNA. Loosely packed chromatin which can be transcribed is referred to as euchromatin.

Analysis of changes in the DNA methylation patterns

Epigenetics

  • Epigenetics is the study of changes in phenotype as a result of variations in gene expression levels
  • Epigenetic analysis shows that DNA methylation patterns may change over the course of a lifetime
  • It is influenced by heritability but is not genetically pre-determined (identical twins may have different DNA methylation patterns)
  • Different cell types in the same organism may have markedly different DNA methylation patterns
  • Environmental factors (e.g. diet, pathogen exposure, etc.) may influence the level of DNA methylation within cells Comparative DNA Methylation Patterns in Twins of Different Ages

7.2.S1 Analysis of changes in the DNA methylation patterns. http://www.pnas.org/content/102/30/10604/F3.expansion.html The images show a mapping of chromosomal regions with differential DNA methylation in monozygotic (identical) twins The sample is of metaphase chromosomes chromosome number (humans have 23 pairs) Similar levels of methylation in both twins. Hypomethylation (low levels of methylation) in one twin compared to the other. Hypermethylation (high levels of methylation) in one twin compared to the other. The diagrams maps changes between the twins’ levels of methylation of DNA across the chromosomes. Your task: compare the diagrams (not the graphs) then analyse the evidence and deduce conclusions.

7.2.U2 Nucleosomes help to regulate transcription in eukaryotes. http://learn.genetics.utah.edu/content/epigenetics/inheritance/images/Reprogramming.jpg Changes in the environment affect the cell metabolism, this in turn can directly or indirectly affect processes such as Acetylation & Methylation. Methylation and acetylation mark the DNA to affect transcription. These these markers are known as epigenetic tags. Reprogramming scours the genome and erases the epigenetic tags to return the cells to a genetic "blank slate”. For a new organism to grow it needs unmarked DNA that can develop into lots of different specialised cell types. For a small number of genes, epigenetic tags make it through this _The branch of genetics concerned with_ process unchanged hence get passed from parent to offspring. hertible changes not caused by DNA is called Epigenetics.

Nature of Science: Looking for patterns, trends and discrepancies - there is mounting evidence that the environment can trigger heritable changes in epigenetic factors. (3.1) http://learn.genetics.utah.edu/content/epigenetics/rats/

Use the excellent Learn.Genetics resources to learn more about Epigenetics and

it’s importance.

What evidence can you find that supports the idea that the environment can

trigger heritable changes?