Biochem Gene Regulation (4)
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Gene regulation in bacteria
- -prevents production of unnecessary material
- -allows rapid response to ever-changing environments
Gene regulation in multicellular organisms
- -creates a developmental program
- -prevents accumulation of excess products that may impair viability
Steps in gene expression that may be regulated Rate of:
- -RNA processing
- -RNA nuclear export (eukaryotes)
- -RNA degradation
- --translation of proteins
- -protein degradation
- -Usually a nucleic acid sequence or structure.
- -Physically linked (part of the same molecule) to the target that is regulated.
- -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.
trans-acting factor(s) binds target and increases gene expression, e.g., increased transcription rate, increased frequency of translation, decreased degradation rate
trans-acting factor(s) binds target and decreases gene expression, e.g., decreased transcription rate, decreased frequency of translation, increased degradation rate
Three co-transcribed genes for lactose utilization, lacZ, lacY, and lacA, plus one gene, lacI, for an essential trans-acting factor.
characteristics of lac operon
- -Not transcribed when lactose absent.
- -Transcribed when lactose present and glucose absent.
- -Not transcribed when lactose and glucose present.
- -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.
cyclic AMP-binding protein (CAP)
- -binds near promoter; increases affinity of RNA polymerase for promoter (cooperative interaction).
- -binds DNA only when complexed with cAMP.
CRE-binding protein (CREB)
binds promoters of genes activated by cAMP, e.g. genes for glucose synthesis
less compact DNA, efficiently transcribed
more compact DNA, limited transcription
cytosine methylation in CpG sequences
contributes to heterochromatin formation; creates binding sites for specific proteins that promote chromatin compaction; silences genes
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
targets proteins to proteasome for degradation
site of protein degradation
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.
the DNA of an individual, differences in DNA between individuals
the consequences of an individual's DNA; differences in appearance, behavior, biochemistry, etc, between individuals
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
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
mutations with (potentially) drastic phenotypic affects
- -creation of a stop codon
- -non-conservative amino acid substitution
- -deletions and insertions
- -disruption in splicing
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