8.2.2 regulation of transcription and translation

what are transcription factors

proteins which regulate transcription of specific target genes in eukaryotes

by binding to a specific DNA base sequence on a promoter region

describe how transcription can be regulated using transcription factors

1. transcription factors move from cytoplasm to nucleus

2. bind to DNA at a specific DNA base sequence on promoter region

3. this stimulates or inhibits transcription of target genes by helping or preventing RNA polymerase binding

explain how oestrogen affects transcription

1. oestrogen is a lipid soluble steroid hormone so diffuses into cell across phospholipid bilayer

2. in cytoplasm, oestrogen binds to receptor an inactive transcription factor forming an oestrogen-receptor complex

3. this changes shape of the inactive transcription factor, forming an active transcription factor

4. the complex diffuses from cytoplasm to nucleus

5. then binds to a specific DNA base sequence on the promoter region of a target gene

6. stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind

explain why oestrogen only affects target cells

other cells do not have oestrogen receptors

what is epigenetics

heritable changes in gene function / expression without changes to base sequence of DNA

caused by changes in the environment

what is epigenome

all chemical modification of DNA and histone proteins - methyl groups on DNA and acetyl groups on histones

what inhibits transcription

increased methylation of DNA

decreased acetylation of histones

what allows transcription

decreased methylation of DNA

increased acetylation of histones

explain how methylation can inhibit transcription

1. increased methylation of DNA - methyl groups added to cytosine bases in DNA

2. so nucleosomes pack more tightly together

3. preventing transcription factors and RNA polymerase binding to promoter

explain how acetylation can inhibit transcription

1. decreased acetylation of histones increases positive charge of histones

2. histones bind DNA more tightly

3. preventing transcription factors and RNA polymerase binding to promoter

explain the relevance of epigenetics in disease development and treatment

environmental factors can lead to epigenetic changes

these can stimulate/inhibit expression of certain genes that can lead to disease development

• increased methylation of DNA or decreased acetylation inhibits transcription

• decreased methylation of DNA or increased acetylation of histones stimulates transcription

diagnostic tests can be developed that detect these epigenetic changes before symptoms present

drugs can be developed to reverse these epigenetic changes

what is RNA interference (RNAi)

inhibits translation of mRNA produced from target genes by RNA molecules e.g. siRNA, miRNA

this inhibits expression of a target gene

where does RNA interference occur

eukaryotes

some prokaryotes

describe regulation of translation by RNA interference

1. small interfering RNA (siRNA) or micro-RNA (miRNA) binds to a protein forming RNA- induced silencing complex (RISC)

   • siRNA synthesised as double stranded RNA - 1 strand incorporated

   • miRNA synthesis as a double stranded hairpin bend of RNA - both strands incorporated

2. single stranded miRNA/siRNA within RISC binds to target mRNA with a complementary base sequence

3. this leads to hydrolysis of mRNA into fragments which are degraded or prevents ribosomes binding

4. reducing/preventing translation of target mRNA into protein