Introduction into the control of gene expression

Question 1

Give an introduction into the control of gene expression

Answer 1

• Genetic estimates indicate that the human genome contains about 50,000 genes.
• In any given cell type only about 10,000 genes are expressed.
• Genome is effectively identical in every cell.
• Genome must be differentially interpreted in different cells at different times.
• Genotype - Human cells all contain the same genetic blueprint.

Question 2

How is differential gene expression tightly regulated?

Answer 2

Differential gene expression is tightly regulated in terms of:
• Time – development (e.g embryos vs adults), in response to hormones, infections and other signals
• Space – differential tissues or cell types express different genes (i.e brain vs muscle cells)

Question 3

Failure to regulate gene expression can lead to?

Answer 3

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Question 4

Describe Drosphilla Homeotic mutants

Answer 4

The Bithorax complex (BX-C) is a group of homeotic genes in Drosophila melanogaster which control the differentiation of the abdominal and posterior thoracic segments, located on chromosome III. When these genes are mutated, the third thoracic segment becomes a repeat of the second thoracic segment, creating what is essentially a second thorax. This can result in a second pair of wings, a second stomach, and duplicated thoracic features in varying degrees.
Antennapedia (abbreviated Antp) is a HOM-C gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae. By contrast gain-of-function alleles convert antennae into ectopic legs.

Question 5

What is the big goal?

Answer 5

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Question 6

Describe beta-thalassemia

Answer 6

• A group of genetic diseases caused by insufficient expression of β -globin.
• In most types of β -thalassaemia the β -globin protein is structurally normal (unlike sickle cell disease).
• Multiple independently arising forms of the disease.
• Mutations causing β -thalassaemia map to multiple sites in the β -globin gene.

Question 7

Describe examples of translational control

Answer 7

• Early embryogenesis – during first 4 – 8 cell divisions there is virtually no gene expression. At the end of blastocyst formation first genes to be expressed are due to up-regulation of translation from maternally-derived pre-formed mRNAs.
• Environmental stress – exposure to heat shock or pathogens can cause global changes in translation.
• Many specific examples – e.g. ferritin.

Question 8

Describe mRNAs and gene expression

Answer 8

mRNAs and the control of gene expression
The 5’ UTR is not the bit that determines whether a ribosome binds, but it DOES play a major role in determining how efficiently the ribosome initiates translation
• Globin (very efficiently translated)
• Ferritin (very inefficiently translated)
• 3’ UTRs confer very different stabilities on mRNAs.
• Globin 3’UTRs confer stability.
• Immune stress hormones (very unstable mRNAs).

Question 9

Describe miRNAs

Answer 9

• The human genome encodes over 500 small non-coding RNAs that are transcribed by RNA polymerase II. These RNAs are referred to collectively as microRNAs or miRNAs.
• These miRNAs act to control the post-transcriptional regulation of as many as one-third of all human genes.
• Any given miRNA can regulate several target genes.
• A miRNA targets a complementary mRNA molecule for destruction.
• Each precursor miRNA transcript is processed to form a double-stranded intermediate, which is further processed to form a mature, single-stranded miRNA. This miRNA assembles with a set of proteins into a complex called RISC, which then searches for mRNAs that have a nucleotide sequence complementary to its bound miRNA. Depending on how extensive the region of complementarity is, the target mRNA is either rapidly degraded by a nuclease within the RISC or transferred to an area of the cytoplasm where other cellular nucleases destroy it.