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Gene Regulation
Bacteria respond to environment
• Must produce or absorb essential
molecules
• Turn on genes when environment is
lacking target molecule
• Turn off genes to save resources when
target molecule is in environment
DNARNA  Protein
Operons
• Operator- switches on a group of adjacent
genes
• Repressor- binds to operator and prevents
transcription
• Repressor is reusable, can attach and
detach from operator
Repressible Operons- usually on
• Tryptophan activates repressor
• Repressor binds to operator
• Gene inactivated
• Tryptophan can come
from either environment or
rom synthesis
Inducible operon- usually off
• Lactose inactivates repressor
• Repressor drops off DNA
• Enzymes are
transcribed
• Once lactose is gone
repressor binds again
Metabolic pathways
• Repressible enzymes  anabolic
pathways
– Build up larger molecules
– Once end product is present pathway turns off
• Inducible enzymes catabolic pathways
– Break down larger molecules
– Turn on in the presence of starting product
Eukaryotic,
multicellular
regulation
• Regulate production of
proteins at any point
during
transcription/translation
Differentiation
• Stem cells can turn into any type of cell
• Zygote = undifferentiated
– All genes are potentially active
• Once a cell differentiates genes are turned
off permanently
• Regulation of genes can occur anywhere
between chromosome and protein function
Regulation of Chromosome
Structure
• Heterochromatin- condensed, not
expressed
• Euchromatin- uncondensed, expressed
• Histone modification
– Acetylation=prevents
histones from binding
to each other
– Creates looser structure
DNA modification
• DNA Methylation
– Addition of methyl groups deactivates DNA
– Blocks RNA polymerase
• Epigenetic Inheritance
– Inheritance of DNA and
chromosome modifications
– Bees (worker vs. queen)
– Potato famine  diabetes
Transgenerational epigenetic observations
See main article Transgenerational epigenetics
In the Överkalix study, Marcus Pembrey and
colleagues observed that the paternal (but not
maternal) grandsons[56] of Swedish men who were
exposed during preadolescence to famine in the 19th
century were less likely to die of cardiovascular
disease. If food was plentiful, then diabetes mortality in
the grandchildren increased, suggesting that this was
a transgenerational epigenetic inheritance.[57] The
opposite effect was observed for females—the
paternal (but not maternal) granddaughters of women
who experienced famine while in the womb (and
therefore while their eggs were being formed) lived
shorter lives on average.[58]
Regulation of Transcription
• Transcription factors bind to DNA, limit
RNA polymerase
• Activators bind
to enhancers,
promote transcription
• Similar to operons
RNA regulation
• RNA processing
– Alternative splicing
• mRNA degradation
– Micro RNA (miRNA) blocks or degrades RNA
– Small interferring RNA (siRNA)
• Regulatory proteins block attachment of
ribosome at 5` end
Protein Regulation
• Polypeptides must be processed before
becoming active proteins
• Lifespan of protein
– Regulatory proteins are short lived
– Tagged with ubiquitin
– Proteosomes degrade tagged
proteins
Non-coding DNA
• 1.5% =exons
• 24%=introns
• 74.5% = repetitive DNA,
non-coding regions,
transposable elements
Transposable elements
•
•
•
•
Segments of DNA that move around
Repeat many times
Function unknown
Alu repeats
– ~300 nucleotides long
– Unique to humans and primates
– Used for DNA fingerprinting
Evolution of the genome
• Earliest life forms had very few genes
– Minimum necessary for survival
• Modern genomes are larger, more
complex
– Non coding regions
– Regulatory genes
– Operons