Regulation Of Gene Expression: Epigenetics

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Epigenetics

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Study of how heritable changes other than these changes in DNA sequence can alter cell and tissue specific patterns of gene expression

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Epigenome

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All the chemical compounds that have been added to the entirety of one's DNA as a way to regulate the activity of all the genes within the genome

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Epigenetic trait

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Stable mitotically and meoitically heretible phenotype that results from changes in gene expression without alterations in DNA sequence

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Epigenitors

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Environmental signals that are received by the cell and that stimulate a response via an intracellular pathway

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Epigenetic initiators

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Responses to epigenitor signals, their actions define the location at which epigenetic changes in chromatin will take place

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Epigenetic maintainers

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Molecular elements that maintain the epigenetic changes that occurred, ensure that the epigenetic modifications are transmitted by mitosis to daughter cells, or by meoisis to daughter cells, or by meoisis to gametes and to subsequent generations

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DNA modification, histone modification, rna interference

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Major epigenetic mechanisms

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CpG islands

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CpG-rich regions in the genome, located at the 5' end of genes usually in promoter regions

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Methyltransferase

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Enzyme that adds methyl group to cytosine in CpG sequences

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Major groove

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Part of DNA structure where methylated CpG occupy

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No Transcription

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What happens: Promoter is methylated

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Lysine, arginine

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Proteins in histone that make them bond easily to phosphate

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H1

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Histone type: lysine-rich

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H2A and H2B

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Histone type: Slightly lysine-rich

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H3 and H4

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Histone type: arginine-rich

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Nucleosome

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Linear array of spherical particles that comprise chromatin fibers. (DNA around histones)

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Solenoid structure

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Nucleosomes further packed to form a thick structure that is heavily dependent on the presence of H1

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Chromatin fiber

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Nucleosomes and solenoid structure further coiled to for a structure 300-nm in diamter

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Acetylation, Methylation, phsophorylation

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Covalent modifications of amino acids in N-terminal histone tails

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Open configuration

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DNA is unmethylated and histones are acetylated

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Closed configuation

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DNA is methylated at CpG islands and histones are deacetylated

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False

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The same type of modification always has the same transcriptional outcome

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True

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Specific combinations of histone modifications control the transcriptional status of a chromatin region

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Histone code

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Sum of complex patterns and interactions of histone modifications and gene expression

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RNA-induced gene silencing

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Short double-stranded RNAs inhibit translation or degrade mRNA in the cytoplasm, or inhibit transcription of genes in nucleus

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siRNA

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Precursor: longer double-stranded rna molecules

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siRNA

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Precursor: located in cytoplasm

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siRNA

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Precursor: results from virus infection, expression of transposon, or introduction into cell by researcher

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MicroRNA

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Precursor: single-stranded RNAs containing a double-stranded stem-loop structure

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MicroRNA

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Precursor: located in nucleus

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MicroRNA

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Precursor: tanscribed from the cell's own genome

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MicroRNA

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Processing: Nucleases within the nucleus cleave the stem-loop structure, which are then transported to the cytoplasm, where they are cut further by Dicer into miRNAs

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siRNA

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Processing: Dicer cleaves precursors into siRNAs

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RITS complex

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Located in the nucleus, it recruits chromatin remodeling proteins that modify chromatin and repress transcription

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RISC

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Complex responsible for dgradation of mRNAs and inhibit translation

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Antisense strand

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Strands used in RISC and RITS as guide strand

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Dicer

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Endoribonuclease protein that cuts RNA into short segments

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Argonaut protein

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Catalyzes cleavage of mRNA, where short double-stranded RNA bind

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Seed

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Part of microRNA that binds to target mRNA

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p53

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Tumor-supprresor gene example

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Proto-oncogene

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Genes that encode proteins that function to stimulate cell division, cell differentiation, and halt cell death

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Histone acetyltransferase

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HAT

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Histone deacetylase

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HDAC

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HDAC

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This changing histone structure converts chromatin into a closed structure

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Szyf and Meaney

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Proponents of studies regarding epigenetics and behavior

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Ex 1:

1. the brains of pups grown by attentive and inattentive mothers are examined

2. Less stressed = rarely methylated (GR), stressed = highly methylated

Ex 3:

1. Pups switched at birth

2. Similar results

Ex 4:

1. Inattentive mother raises pups

2. Pups injected with trichostain A, removes methyl groups

3. Epigenetic changes disappear

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Epigenetics and Behavior study steps

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1. Pregnant mice given BPA, decrease in methylation of agouti gene, yellow offspring

2. Pregnant mice given BPA with vitamin B cocktail, increase in methylation of agouti gene, have brown offspring

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Epigentics and environment steps

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1. RNA binds to argonaut protein

2. Guide strand is selected from double stranded rna and binds to argonaut

3. Forms complex RISC

4. siRNA direct RISC to specific mRNA

5. miRNA guide RISC to hundreds of endogenous mRNA

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RNA interference: mRNA stability (RISC)

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siRNA:

1. Precursor introduced in cytoplasm

2. Cleaved into siRNA by dicer

MicroRNA:

1. Transcribed by gene

2. Stem loop is cleaved by nuclease

3. Transported to cytoplasm and is cleaved into microRNA by dicer

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Precursor processing steps

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1. si/miRNA associates with RITS complex

2. Antisense strand is used to locate gene promoters/larger regions of chromatin

3. RITS recruits chromatin remodelling enzymes

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How RITS works