本文選題：豬肺泡巨噬細(xì)胞　切入點(diǎn)：Poly(I:C)　出處：《華中農(nóng)業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：豬肺泡巨噬細(xì)胞(PAM)作為機(jī)體重要的免疫細(xì)胞,在抵抗病原入侵和免疫應(yīng)答方面發(fā)揮著重要的作用。有研究表明等位基因的特異性表達(dá)與某些易感疾病的發(fā)生緊密相關(guān),但是在PAM細(xì)胞中探究等位基因特異性表達(dá)與疾病、免疫相關(guān)的進(jìn)展還不是很多,并且關(guān)于等位基因特異性表達(dá)的調(diào)控機(jī)制研究的也不是很透徹。因此,本論文將圍繞豬肺泡巨噬細(xì)胞系3D4/21在受到Poly(I:C)刺激前后等位基因的特異性表達(dá)情況以及可能受到的轉(zhuǎn)錄調(diào)控因素,如轉(zhuǎn)錄因子結(jié)合、組蛋白修飾以及單倍型染色質(zhì)交互差異等方面展開分析,主要結(jié)果如下:基于RNA-seq數(shù)據(jù),分別鑒定出PAM細(xì)胞系3D4/21在受到Poly(I:C)刺激和未刺激情況下具有偏好性表達(dá)的等位基因,經(jīng)過綜合比較,發(fā)現(xiàn)有一些與病原感染、免疫應(yīng)答相關(guān)的等位基因在刺激后呈現(xiàn)出了不同的表達(dá)偏好性并且其總的表達(dá)量相比于未刺激的情況下顯著升高,我們推測這些基因含有抵抗病原體入侵的相關(guān)突變,可作為候選的疾病抗性基因進(jìn)行下步實(shí)驗(yàn)驗(yàn)證。為了進(jìn)一步理解等位基因不平衡表達(dá)的相關(guān)調(diào)控機(jī)制,我們結(jié)合ChIP-seq數(shù)據(jù)進(jìn)行關(guān)聯(lián)分析,結(jié)果表明轉(zhuǎn)錄因子結(jié)合和組蛋白修飾的單倍型偏好性與等位基因表達(dá)的偏好性高度相關(guān)。而且我們通過在單倍型水平上觀察CTCF,RNAPII介導(dǎo)的染色質(zhì)交互信息,可以看到單倍型染色質(zhì)交互的偏好性與等位基因表達(dá)的偏好性也具有一致性。我們的研究結(jié)果對于探索提高豬抗病能力和免疫能力提供了一些有益的啟示,對于理解等位基因的特異性表達(dá)及相關(guān)調(diào)控因素的關(guān)系具有一定的參考意義。
[Abstract]:As an important immune cell, porcine alveolar macrophage (PAM) plays an important role in resisting pathogen invasion and immune response. Some studies have shown that the specific expression of allele is closely related to the occurrence of some susceptible diseases. However, there is not much progress in exploring the relationship between allele-specific expression and disease in PAM cells, and the regulation mechanism of allele-specific expression is not very thorough. This paper will focus on the specific expression of alleles in porcine alveolar macrophage cell line 3D4 / 21 before and after stimulation by Polynei: C and the possible transcriptional regulatory factors, such as transcription factor binding. Histone modification and haplotype chromatin interaction were analyzed. The main results were as follows: based on RNA-seq data, the alleles of PAM cell line 3D4 / 21 were identified with preference expression under and without stimulation of PAM cell line 3D4 / 21, respectively. After comprehensive comparison, we found that some alleles associated with pathogen infection and immune response showed different expression preferences after stimulation, and the total expression of these alleles was significantly higher than that without stimulation. We speculate that these genes contain mutations related to resistance to pathogen invasion, which can be used as candidate disease resistance genes for next step experiments. In order to further understand the related regulation mechanism of unbalanced expression of alleles, We use the ChIP-seq data to do the association analysis, The results showed that the haplotype preference of transcription factor binding and histone modification was highly correlated with the preference of allelic expression, and we observed the chromatin interaction mediated by CTCF RNAPII at the haplotype level. It can be seen that the preference of haplotype chromatin interaction is also consistent with that of allelic expression. It has some reference significance for understanding the specific expression of alleles and the relationship between related regulatory factors.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：S852.4;Q811.4

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本文編號：1593450