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首頁> 外文OA文獻(xiàn) >An integrative bioinformatics approach for analyses of multi-level transcriptional regulation and three-dimensional organization in the epidermis and skin appendages. Exploring genomic transcriptional profiles of the distinct stages of hair follicle and sweat gland development and analyses of mechanism integrating the transcriptional regulation, linear and high-order genome organization within epidermal differentiation complex in keratinocytes.
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An integrative bioinformatics approach for analyses of multi-level transcriptional regulation and three-dimensional organization in the epidermis and skin appendages. Exploring genomic transcriptional profiles of the distinct stages of hair follicle and sweat gland development and analyses of mechanism integrating the transcriptional regulation, linear and high-order genome organization within epidermal differentiation complex in keratinocytes.

機(jī)譯:一種綜合生物信息學(xué)方法,用于分析表皮和皮膚附件的多級轉(zhuǎn)錄調(diào)控和三維組織。探索毛囊和汗腺發(fā)育不同階段的基因組轉(zhuǎn)錄概況,并分析角質(zhì)形成細(xì)胞表皮分化復(fù)合物中轉(zhuǎn)錄調(diào)控,線性和高級基因組組織的整合機(jī)制。

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摘要

The transcription in the eukaryotic cells involves epigenetic regulatoryudmechanisms that control local and higher-order chromatin remodelling. In theudskin, keratinocyte-specific genes are organized into distinct loci includingudEpidermal Differentiation Complex (EDC) and Keratin type I/II loci. This thesisudintroduces bioinformatics approaches to analyze multi-level regulatoryudmechanisms that control skin development and keratinocyte-specificuddifferentiation.udFirstly, integration of gene expression data with analyses of linear genomeudorganization showed dramatic downregulation of the genes that compriseudlarge genomic domains in the sweat glands including EDC locus, compared toudiiudhair follicles, suggesting substantial differences in global genome rearrangementudduring development of these two distinct skin appendages.udSecondly, comparative analysis of the genetic programmes regulated inudkeratinocytes by Lhx2 transcription factor and chromatin remodeler Satb1udrevealed that significant number of their target genes is clustered in theudgenome. Furthermore, it was shown in this study that Satb1 target genes areudlineage-specific.udThirdly, analysis of the topological interactomes of Loricrin and Keratin 5 inudhair follicle steam cells revealed presence of the cis- and trans-interactionsudand lineage specific genes (Wnt, TGF-beta/activin, Notch, etc.). Expressionudlevels of the genes that comprise interactomes show correlation with theirudhistone modification status.udThis study demonstrates the crucial role for integration of transcription factormediatedudand epigenetic regulatory mechanisms in establishing a properudbalance of gene expression in keratinocytes during development anduddifferentiation into distinct cell lineages and provides an integratedudbioinformatics platform for further analyses of the changes in globaludorganization of keratinocyte-specific genomic loci in normal and diseasedudskin.
機(jī)譯:真核細(xì)胞中的轉(zhuǎn)錄涉及控制局部和更高階染色質(zhì)重塑的表觀遺傳調(diào)控 ud機(jī)制。在 udskin中,角質(zhì)形成細(xì)胞特異性基因被組織成不同的基因座,包括 udEpidermadifferent Complex(EDC)和Keratin I / II型基因座。本論文介紹了生物信息學(xué)方法來分析控制皮膚發(fā)育和角質(zhì)形成細(xì)胞特異化/多分化的多級調(diào)節(jié)機(jī)制。 ud首先,基因表達(dá)數(shù)據(jù)與線性基因組分析的整合未組織化顯示了構(gòu)成超大基因的顯著下調(diào)與 udii udhair卵泡相比,包括EDC基因座在內(nèi)的汗腺中的基因組區(qū)域,提示在全球基因組重排中在這兩個(gè)不同的皮膚附件發(fā)育過程中存在實(shí)質(zhì)性差異。 udd,第二,對Lhx2調(diào)控 uderatinatinocytes的遺傳程序的比較分析。轉(zhuǎn)錄因子和染色質(zhì)重塑劑Satb1 ureveveal表示,它們的大量目標(biāo)基因聚集在預(yù)算中。此外,這項(xiàng)研究表明,Satb1靶基因是 udlineage特有的。 ud第三,對Loricrin和Keratin 5在烏頭毛囊蒸汽細(xì)胞中的拓?fù)湎嗷プ饔玫姆治霰砻?,存在順式和反式相互作?udand譜系特定基因(Wnt,TGF-β/激活蛋白,Notch等)。組成相互作用基因的基因的表達(dá) ud水平與其 udhistone修飾狀態(tài)相關(guān)。 ud這項(xiàng)研究證明了轉(zhuǎn)錄因子介導(dǎo)的 ud和表觀遺傳調(diào)控機(jī)制的整合對于在發(fā)育和形成角質(zhì)形成細(xì)胞中適當(dāng)?shù)幕虮磉_(dá)失衡起著至關(guān)重要的作用。 uddiffentiation成不同的細(xì)胞譜系,并提供了一個(gè)集成的 udbioinformatics平臺,用于進(jìn)一步分析正常和患病的 udskin中角質(zhì)形成細(xì)胞特異性基因組基因的全球 udorganization的變化。

著錄項(xiàng)

  • 作者

    Poterlowicz K.;

  • 作者單位
  • 年度 2013
  • 總頁數(shù)
  • 原文格式 PDF
  • 正文語種 en
  • 中圖分類

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