epigenetika - university of ljubljana · • genomski imprinting • razlike v konformaciji...
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Epigenetikain vedenjske lastnosti
Prof. dr. Peter DOVČOddelek za zootehnikoBiotehniška fakulteta
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Kaj je epigenetika?
• Genetika• Genomika• Epigenetika• Epigenomika
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Nekaj dokazov za obstoj epigenetskih mehanizmov
• Diferenciacija celic • Razlike med enojajčnimi dvojčki• Razvojne spremembe v izražanju genov• Genomski imprinting• Razlike v konformaciji kromatina (DnaseI)
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Callipyge – polar overdominance
The mutation responsible for the callipyge trait is located within an imprinted gene cluster on the distal end ofovine chromosome 18. The callipyge phenotype is inherited in a non-Mendelian mode termed polarOverdominance in which only animals that inherit a normal allele (wild type; +) from the dam and the mutant callipyge allele from the sire (CLPGPat) exhibit the callipyge phenotype. Maternal heterozygotes(CLPGMat/+Pat) and callipyge allele homozygotes (CLPGMat/CLPGPat) have muscling and carcasscompositions that are similar to normal sheep (wild type homozygotes; +/+).
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H19/Igf2 imprinting
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Epigenetika in izražanje genov
• Uravnavanje izražanja genov na različnih stopnjah– Transkripcija– Posttranskripcijske spremembe– Translacija– Posttranslacijske spremembe– Interakcija z okoljem (inducibilnost)
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Metilacija DNA
• Metilacija 5’-citozina• Metilacija promotorskih regij
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DNA metiltransferaze (DNMT)
• Sesalci imajo 4 DNMT• DNMT1 - vzdržuje vzorec metilacije• DNMT2 – šibko delovanje in vitro,
metilacija RNA• DNMT3a,b – de novo metilacija
• Demetilacija: počasna pasivna in hitra aktivna demetilacija – povezana s popravljalnimi mehanizmi.
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DNMT in transkripcijski faktorji
• Specifično metilacijo omogoča povezava med DNMT in transkripcijskimi faktorji
• Sterična inhibicija
• Vezava proteinov, ki prepoznavajo metilno skupino
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DNA metilacija in proteini, ki se vežejo na metilno skupino
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Histoni in uravnavanje genskega izražanja
• Metilacija histonov(HMT: arginin, lizin)
• Histonskeacetiltransferaze
• Histonskedeacetiltransferaze
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ncRNA
• siRNA• lnRNA
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So epigenetski vzorci dedni?
• Delovanje DNMT1• Embrionalni razvoj
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Epigenetika in vedenje
Mišji model inducibilnega anksioznega vedenja
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Ciljno inducirano izražanje KAP1