Biology Chapter 13 Regulation Of Gene Expression

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Connection Between Gene Regulation and Physiology and Behavior in Primates

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- Showed that higher-status female macaque primates had stronger immune systems and genes that were expressed differently (meaning different genes were turned on and off) than lower-status female macaques

- Shows that many factors, including social status can control gene expression

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Operon Model

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- Proposed by Francois Jacob and Jacques Monod to explain regulation of gene expression in prokaryotes

- ____________ is a group of structural and regulatory genes that function as a single unit

- Enzymes are produced as needed

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Promotor

Operator

Structural Genes

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3 Components of Operon

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Promotor

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- DNA sequence where RNA polymerase first attaches, short segment of DNA

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Operator

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DNA sequence where active repressor binds, short segment of DNA

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Structural Genes

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- One to several genes coding for enzymes of a metabolic pathway

- Transcribed simultaneously as a block

- Long segment of DNA

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Regulatory Gene

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- Codes for a repressor protein that controls the operon

- Normally located outside the operon

- Repressor protein controls whether the operon is active or not

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- Repressor is unable to attach to the operator (expression is normally "on")

- RNA polymerase binds to the promotor

- Which triggers production of enzymes for synthesis

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3 things if tryptophan is absent (trp Operon)

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- trp combines with repressor protein as its corepressor

- Repressor becomes functional so blocks synthesis of enzymes in the pathway for tryptophan synthesis

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2 things if tryptophan trp Operon is present

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- If lactose (sugar for food) is absent, repressor attaches to the operator (expression is normally "off"

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When lactose lac operon is absent

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- Lac operon combines with repressor and renders it unable to bind with operator

- RNA polymerase binds to promotor

- Triggers production of 3 enzymes necessary for lactose catabolism

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If lac operon lactose is present, 3 things that happen

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E Coli

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- Disease that preferentially breaks down glucose

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When glucose is absent in prokaryotic regulation

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- Without ________, lac operon is maximally activated

- cAMP accumulates, binds to catabolite activator protein, together binds to site near lac promotor

- When bound, RNA polymerase binds better to promotor

- Structural genes of lac operon are expressed more efficiently

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Nuclear Levels

- Chromatin Structure

- Transcriptional Control

- Posttranscriptional Control

Cytoplasmic Levels

- Translational Control

- Posttranslational Control

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Eukaryotic Regulation there are a variety of mechanisms

5 Primary levels of control

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Chromatin

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- Eukaryotic DNA is associated with histone proteins to make up what?

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Nucleosomes

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DNA is wound around groups of 8 histone proteins and looks like beads on a string

- What are these beads called?

- Levels of chromatin packing are determined by degree of _______ coiling

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Euchromatin

Heterochromatin

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- Loosely coiled and transcriptionally active

- Tightly packed and transcriptionally inactive

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Barr Body

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- Of the two X chromosomes of the female, the tightly packed inactive X chromosome

Ex: Calico Cat

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Epigenetic inheritance

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- Refers to inheritance patterns not dependent on genes themselves and explains unusual inheritance patterns

- May also play a role in growth, aging and cancer

Ex: Histone modification where variations in the pattern of inheritance is not due to changes in the sequence of DNA nucleotides

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Transcriptional Control

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- Controlled by proteins called transcription factors which help regulate transcription by assisting the binding of the RNA polymerase to the promoter

- Transcriptional activator is a DNA binding protein that binds to enhancer DNA, regions of DNA where transcription factors can also bind

- Always present in the cell, but most likely have to be activated before they will bind to DNA

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Posttranscriptional Control

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- Operates on the primary mRNA transcript, where excision of introns and splicing of exons can vary

- Control speed of mRNA transport out of nucleus by affecting number of transcripts arriving at rough ER, thus amount of gene product

Ex: Hypothalamus and thyroid release different versions of calcitonin

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sRNA (small RNA)

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- Noncoding transcribed DNA used to form _____ which are involved in gene regulation and function at multiple levels of gene expression

- Regulate transcription and translation

- Source of microRNAs (miRNA) regulating translation by causing destruction of mRNAs before they can be translated

- Source of small interfering (siRNA) that form silencing complex that targets specific mRNAs for breakdown, preventing expression

- Referred to as RNA interference

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microRNA (miRNA)

small-interfering RNA(siRNA)

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sRNA molecules source 2 types of RNA that help in RNA interference

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microRNA miRNA

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- Regulates translation by causing the destruction of mRNAs before they can be translated

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small-interfering RNA siRNA

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- Form a silencing complex that targets specific mRNAs for breakdown, preventing their expression

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Translational Control

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- Determines the degree to which mRNA is translated into protein product

- The presence of the 5' cap and length of poly A tail on 3' end of the mRNA affect whether translation occurs or how long mRNA remains active

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Posttranslational control

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- Affects activity of protein product

- Accomplished by regulating activation and degradation rate

- Proteases are enzymes that break down proteins and by doing so help regulate gene expression - how long protein remains active or confined to proteasome or lysosomes to protect cell

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Gene Mutation

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- Permanent change in the sequence of bases in DNA

- Effects can range from no effect to complete inactivation of the protein

- Germ-line mutations in sex cells

- Somatic mutations in body cells

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Spontaneous mutation

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- Chemical changes in DNA that lead to mispairing during replication

- Movement of transposons from one chromosomal location to another

- Replication Errors from DNA polymerase 1/ 1,000,000,000

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Induced mutations

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- Caused by mutagens such as radiation, carcinogens and organic chemicals

- Environment mutagens include UV radiation and tobacco smoke

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Point Mutation

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- Example: Base substitution which involves change in a single DNA nucleotide, changing one codon to a different codon

- Effects on the protein vary from being nonfunctional, reducing it or not affecting it

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Frameshift Mutations

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- 1 or 2 nucleotides are either inserted or deleted from DNA

- Protein is always rendered nonfunctional

- Results in different reading frame for the codons

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Proto-Oncogenes

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- Stimulate cell division

- Mutated versions are always active

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Tumor Suppressor Genes

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- Inhibit cell division

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Cancer

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- Development involves a series of accumulating mutations

- Oncogenes and mutations in tumor suppressor genes lead to tumor formation

- Stimulate the cell cycle uncontrollably

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Nonfunctional Proteins

Faulty Enzyme

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- If inserted into metabolic pathway, a personal may be unable to convert one molecule to another with serious consequences

-Ex: Phenylketonuria: Excess buildup causes intellectual disability

-Ex: Androgen insensitivity: Cells unable to respond to testosterone so female genitals and characteristics occur at puberty

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Transcriptional Control

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- Transcription factors bind to promoters

- Transcription activators bind to enhancers

- Mediator proteins bind transcription activators to transcription factors

- RNA polymerase begins transcribing

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Transcription Activator

Transcription Factor

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2 proteins required for transcription initiation by RNA polymerase

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DNA repair enzymes

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- Remove damaged DNA

- Seal new DNA into a preexisting DNA strand

- Make new section of DNA

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Spontaneous Mutation Causes

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- Chemical Change of a base

- DNA replication

- Transposon movement

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Possible consequences of mutated DNA gene?

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- Different protein product

- Different genotype

- Different phenotype

- Different mRNA transcript

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Enhancer

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Region of DNA that acts as regulatory element through binding with transcription activators

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Promoter

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Binds with transcription factors

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Mediator Proteins

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Acts as a bridge between transcriptional factors and transcription activators

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Transcription Factors

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- Proteins that help regulate transcription by assisting the binding of RNA polymerase to the promotor