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GENE EXPRESSION

How does a bone cell know to transcribe the genes


that control the synthesis of collagen and not to
transcribe genes that specify muscle proteins?

What causes the proportions of blood cells types to


shift into leukemia?

How do chemical groups know to shield DNA from


transcription in one circumstance, yet expose it to
others?
EPIGENETICS
Changes to the chemical groups that associate with
DNA that greatly affects which part of the genome are
accessible to transcription factors and under which
conditions

Changes to the molecules that bind to DNA that are


transmitted to daughter cells when the cell divides

outside the gene


E.g. methyl groups bind to DNA

Do not alter the DNA base sequence

Reversible

Passed from one cell generation to the next

Changes may affect the next generation of individuals


if the conditions to which a fetus is exposed become
dangerous
2 Examples of Gene Expression

1. Hemoglobin switching during


development

2. Specialization of the two major parts of the


pancreas
Globin Chain Switching

Globin proteins transport oxygen in the blood

Control gene expression via globin chain switching

Assemble into different hemoglobin molecules


depending upon stage of development
Embryo: 2(Epsilon) 2 (Zeta)

Fetus: 2 2

Adult hemoglobin: 2 2 polypeptide chains


Building Tissues and Organs

Solid gland or organ

Distinctive 3 dimensional form

Constructed from specialized cells and in many


cases more than one type of tissue

More complex than blood


Specific, solid organization must be maintained
throughout life

Cells must maintain their specialization

Genes are turned on and off during development, as


stem cells self renew and yield more specialized
daughter cells
Pancreas

Dual gland

2 types of cell clusters

Exocrine part releases digestive enzymes

Endocrine part secretes polypeptide hormones


that control nutrient use directly into the
bloodstream
A transcription factor is activated and controls
expression of other genes in a way that stimulates
some progenitor cells to divide

Certain daughter cells follow an exocrine pathway

Other progenitor cells respond to different signals and


divide to yield daughter cells that follow the endocrine
pathway
Control of Gene Expression
A. Chromatin Remodelling

- Histone proteins associated with DNA interact with


other chemical groups in ways that expose some
sections of DNA to transcription factors and shield
other sections, blocking their expression
3 major types of small molecules that bind to histone:

1. Acetyl groups

2. Methyl groups

3. Phosphate groups
1. Acetyl Groups (CH3CO2)

Bind to very specific sites, particularly to the amino acid lysine

Can shift histone interactions in a way that allows


transcription to begin

A series of proteins moves the histone complex away from the


TATA box, exposing it enough for RNA polymerase to bind to
start transcription

Deacetylases remove acetyl groups which shuts off gene


expression
2. Methyl Groups (CH3)

Also added to or taken away from histones

Binds to a specific amino acid in a specific histone


type, a protein is attracted that prevents
transcription

Gene silencing
B. microRNAs

Act later in gene expression

prevents the translation of mRNA transcripts into


protein

dimmer switch, fine-tuning gene expression at a


later stage
Application:

Certain microRNAs are either more or less abundant in


cancer cells than in healthy cells

Restoring the levels of microRNAs that normally


suppress the too-rapid cell cycling of cancer, or
blocking production of microRNAs that are too
abundant in cancer, could help to return cells to a
normal cell division rate
Maximizing Genetic Information
Only a small part of the genome encodes proteins,
1.5% of human DNA

Alternate splicing, use of introns, protein


modification, and cutting proteins translated from a
single gene contribute to protein diversity
Non-protein encoding part of the genome:

- viral sequences
- non-coding RNAs (tRNAs, rRNAs)
- pseudogenes
- introns
- transposons
- promo0ters
- other controls & repeats

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