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Gene regulation in bacteria
- -prevents production of unnecessary material
- -allows rapid response to ever-changing environments
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Gene regulation in multicellular organisms
- -creates a developmental program
- -prevents accumulation of excess products that may impair viability
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Steps in gene expression that may be regulated Rate of:
- -transcription
- -RNA processing
- -RNA nuclear export (eukaryotes)
- -RNA degradation
- --translation of proteins
- -protein degradation
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cis-acting element
- -Usually a nucleic acid sequence or structure.
- -Physically linked (part of the same molecule) to the target that is regulated.
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trans-acting factor
- -Usually a protein that binds a cis-acting sequence.
- -Free to move in the cell; binding activity may be modified by small molecule, phosphorylation, etc.
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positive control
trans-acting factor(s) binds target and increases gene expression, e.g., increased transcription rate, increased frequency of translation, decreased degradation rate
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negative control
trans-acting factor(s) binds target and decreases gene expression, e.g., decreased transcription rate, decreased frequency of translation, increased degradation rate
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lac operon
Three co-transcribed genes for lactose utilization, lacZ, lacY, and lacA, plus one gene, lacI, for an essential trans-acting factor.
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characteristics of lac operon
- -Not transcribed when lactose absent.
- -Transcribed when lactose present and glucose absent.
- -Not transcribed when lactose and glucose present.
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lac repressor
- -binds to specific DNA sequence called the operator.
- -binding physically prevents RNA polymerase binding to promoter.
- -binds operator in absence of lactose.
- -binds lactose and dissociates from DNA.
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cyclic AMP-binding protein (CAP)
- -binds near promoter; increases affinity of RNA polymerase for promoter (cooperative interaction).
- -binds DNA only when complexed with cAMP.
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CRE-binding protein (CREB)
binds promoters of genes activated by cAMP, e.g. genes for glucose synthesis
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euchromatin
less compact DNA, efficiently transcribed
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heterochromatin
more compact DNA, limited transcription
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cytosine methylation in CpG sequences
contributes to heterochromatin formation; creates binding sites for specific proteins that promote chromatin compaction; silences genes
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lysine acetylation in N-termini of histones
- -contributes to euchromatin formation by weakening interaction w/DNA (loss of positive charge)
- -acts over a region of a gene or a chromosome
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ubiquitin
targets proteins to proteasome for degradation
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proteasome
site of protein degradation
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genetic variation explains why:
- -only some individuals develop a particular disease.
- -individuals differ in their innate ability to conquer a disease.
- -the effectiveness of a particular drug varies among individuals.
- -the side-effects of a particular drug varies among individuals.
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genotype
the DNA of an individual, differences in DNA between individuals
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phenotype
the consequences of an individual's DNA; differences in appearance, behavior, biochemistry, etc, between individuals
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Mutations with no phenotypic consequences
- -changes in non-coding DNA (e.g. repetitive sequences, introns)
- -changes in "wobble" bases (3rd position) in many codons
- -changes in genes that aren't transcribed in a given cell
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mutations with (potentially) minor phenotypic affects
- -"conservative" amino acid substitutions (e.g. mutations in some 1st positions)
- -alterations in regulatory sequences
- -loss of gene function when second copy is normal and sufficient
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mutations with (potentially) drastic phenotypic affects
- -creation of a stop codon
- -non-conservative amino acid substitution
- -frameshift
- -deletions and insertions
- -disruption in splicing
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