8.3: Regulation of transcription and translation

What is a transcription factor?

Proteins which regulate transcription of specific target genes in eukaryotes by binding to specific DNA base sequences on promoter regions, either activating or repressing the transcription of a particular gene

What is transcriptional regulation?

The control of gene expression by preventing or promoting the transcription of DNA into RNA, usually through transcription factors binding to promoter regions

How is transcription regulated using transcription factors?

• Transcription factors move from the cytoplasm to the nucleus

• They bind to DNA at a specific DNA base sequence on a promoter region

• This stimulates/inhibits transcription of target genes by helping or preventing RNA from binding

Label the diagram

• Cluster of transcription factors on promoter region- transcription initiation complex

• Intron

• Gene

How does oestrogen initiate transcription?

• Oestrogen diffuses directly across the phospholipid bilayer as it is a lipid-soluble steroid hormone

• In the cytoplasm, oestrogen binds to a receptor site on a specific transcription factor, forming an oestrogen-receptor complex

• This causes a conformational change of the DNA binding site of the transcription factors

• The oestrogen-receptor complex diffuses from the cytoplasm into the nucleus

• It then binds to a specific DNA base sequence on the promoter region of a target gene

• This stimulates transcription of target genes by forming mRNA by helping RNA polymerase to bind

• Therefore the gene is transcribed and expressed

Why does oestrogen only affect target cells?

Other cells do not have oestrogen receptors

What is epigenetics?

Changes to DNA that alters the expression of genes without changes to the base sequences of DNA, which can be inheritable or caused by environmental changes

What is the epigenome?

All possible chemical modifications of DNA and histone proteins that regulate gene expression without changing the underlying DNA sequence

What is heterochromatin?

• Tightly packed chromatin associated with histones

• It is silenced as it cannot be accessed by RNA polymerase and transcription factors

What is euchromatin?

• Loosely bound chromatin associated with histones

• It can be expressed as it is more accessible to RNA polymerase and transcription factors

Summarise the epigenetic control of gene expression in eukaryotes

• To inhibit transcription: DNA methylation increased, Histone acetylation decreased

• To allow transcription: DNA methylation decreased, Histone acetylation increased

How can methylation inhibit transcription?

• Methyl groups are added to DNA at specific locations (CpG) sites by methyltransferase

• CpG sites is where cytosine is next to guanine in the DNA chain

• DNA methylation prevents transcription factors from binding to the DNA, so RNA polymerase cannot bind so gene cannot be transcribed

• So transcription is always inhibited

• (Methyl groups can also be removed in demethylation so effect would be in reverse)

How can acetyl groups promote transcription?

• Acetyl groups are added directly to the lysine amino acid on histones by acetyl coenzyme A

• Acetylation neutralised the positive charge of lysine, reducing attraction between DNA and histones

• So histones bind to DNA less tightly, becoming euchromatin

• This stimulates transcription factors and RNA polymerase to bind to promoter regions

• So genes are transcribed

• (Acetyl groups can also be removed in deacetylation so effect would be in reverse)

What is RNA interference?

• Inhibition of translation of mRNA produced from target genes, by RNA molecules such as siRNA

• This inhibits expression of a target gene

Describe the regulation of translation by RNA interference

• Small interfering RNA (siRNA) is incorporated into a protein, forming an RNA induced silencing complex (RISC)

• siRNA is synthesised as double stranded RNA with one strand incorporated

• Single stranded siRNA within the RISC binds to target mRNA with a complementary base sequence

• This leads to hydrolysis of mRNA into fragments which prevents ribosomes from binding

• Preventing translation of target mRNA into a protein

Why is RNAi sequence-specific?

siRNA binds only to mRNA with a complementary base sequence