Epigenetikus reguláció a Drosophila melanogaster bithorax komplexében= Epigenetic regulation in the bithorax complex of Drosophila melanogaster (original) (raw)

Abstract

Fontosabb eredmenyek Kimutattuk, hogy a bithorax komplexben (Bx-C) a Polycomb Response Elementek (PRE-k), es a hozzajuk kapcsolodo Polycomb feherjek nemcsak a cisz-regulator regiok inaktiv/zart allapotanak fenntartasaban jatszanak fontos szerepet, hanem az aktiv/nyilt allapotu cisz-regulatorokban talalhato enhanszerek hatasanak modulalasaban is. Ezt a hatas ugy fejti ki, hogy fizikailag a celgen promoterehez kotődik. Ezzel osszefuggesben kimutattuk egy, a bxd PRE-vel reszben atfedő Targetalo Elem (TE) jelenletet. A TE a PRE-hez hasonloan modularis szerkezetű. Igazoltuk, hogy ez az elem nemcsak a PRE promoterhez valo kőtődeseben jatszik szerepet, hanem reszt vesz a bxd regioban talalhato enhanszereknek az Ubx promotere kore valo szervezeseben, azaz az „acticve chromatin hub” kialakitasaban. A TE ezt a funkciojat ektopikus kornyezetben, az iab-7 cisz regulatorban is megőrzi. A PRE-től hatarolo elemmel elvalasztott bxd enhanszerek ektopikus aktivitast mutatnak, amely mind fenotipus analizissel, mind markergen expressziojanak kovetesevel kimutathato. Kinutattuk, hogy az ebi gen a Polycomb csoport genjei koze sorolando, es a polyhomeotic gennel egyutt az aktiv allapotu cisz-regulatorokban fejti ki modulalo hatasat. Kvantitativ RTPCR segitsegevel kimutattuk, hogy az Abd-B RNS mennyisege korulbelul duplajara nő polyhomeotic mutans hatteren. | We showed that Polycomb Response Elements (PREs) and Polycomb proteins bound to them play an important role not only in maintaining inactive/closed conformation of cis-regulatory elements in the bithorax complex, but they are also involved in modulating the regulatory output of enhancers in the active/open domains. This latter effect is mediated by direct physical contact between the PRE and the promoter – enhancer complex. In connection with this we demonstrated the presence of a Targeting Element (TE) that partially overlaps with the bxd PRE. TE is, similarly to the PRE, modularly organized. We showed that this element is involved not only in targeting the PRE to the Ubx promoter, but also part of the machinery organizing the active chromatin hub around cognate promoter. We also demonstrated that the TE maintains its activity in ectopic context, in the iab-7 cis-regulatory region. Enhancers separated from the bxd PRE by a boundary region exhibit ectopic activity, as revealed by both phenotypic analysis and by monitoring the expression pattern of a marker gene. We identified the ebi gene as an unusual Polycomb group member, which, similarly to the polyhometic gene, participates in the modulation of enhancer output of active cis-regulatory regions. Using quantitative RTPCR we showed that the amount of the Abd-B RNA is doubled in polyhomeotic mutant background.

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