DNA methylation-histone modification relationships across the desmin locus in human primary cells.
DNA methylation-histone modification relationships across the desmin locus in human primary cells.
复制标题
DOI：
10.1186/1471-2199-10-51
复制
发表时间：
2009-05-27
影响因子：
--
通讯作者：
Antoniou M
中科院分区：
文献类型：
--
作者：
Lindahl Allen M;Koch CM;Clelland GK;Dunham I;Antoniou M
我们在这里提出了一个500kb区域的广泛的表观遗传学分析，它包括人类结蛋白基因(DES)及其5‘位点控制区(LCR)，这是迄今为止所描述的唯一的肌肉特异性转录调控元件。这些数据补充和扩展了DNA元素百科全书(ENCODE)关于ENr133区域的研究。我们分析了生理上相关的DES表达(成肌细胞/肌管)和不表达(外周血单核)的原代人类细胞中的组蛋白修饰和潜在的DNA甲基化模式。我们发现，在表达成肌细胞/肌管而不是外周血单个核细胞(PBMC)的培养中，组蛋白H4乙酰化表现出广泛分布的富含200kb基因的区域，而H3乙酰化则定位于基因的转录起始点(TSS)。我们发现，DES的DES、LCR和TSS富含乙酰化组蛋白H3的超乙酰化结构域，H3赖氨酸4二甲基化和三甲基化(H3K4me2和ME3)在该基因座上表现出不同的分布模式。延伸到DES第一内含子的CpG岛是无甲基化的，无论基因的表达状态如何，在非表达的PBMC中，组蛋白H3赖氨酸27三甲基化(H3K27me3)被标记。总体而言，我们的结果构成了第一个将组蛋白修饰模式与肌肉特异性LCR及其相关下游基因区域的潜在DNA甲基化联系起来的研究，同时还将其置于更广泛的基因组背景下。我们的结果清楚地表明，在DES LCR、启动子和基因内区存在不同的组蛋白H3和H4乙酰化和H3甲基化模式。此外，H3K27me3仅在非表达的PBMC中存在于DES甲基化非甲基化的CpG处，这可能有助于在非肌肉组织中沉默该基因。总的来说，我们的工作证明了在研究表观遗传标记时，使用代表不同表达/非表达状态的多种生理相关组织类型的重要性，以及在研究染色质结构时，潜在的DNA甲基化状态应该与组蛋白修饰模式相关。
We present here an extensive epigenetic analysis of a 500 kb region, which encompasses the human desmin gene (DES) and its 5' locus control region (LCR), the only muscle-specific transcriptional regulatory element of this type described to date. These data complement and extend Encyclopaedia of DNA Elements (ENCODE) studies on region ENr133. We analysed histone modifications and underlying DNA methylation patterns in physiologically relevant DES expressing (myoblast/myotube) and non-expressing (peripheral blood mononuclear) primary human cells. We found that in expressing myoblast/myotube but not peripheral blood mononuclear cell (PBMC) cultures, histone H4 acetylation displays a broadly distributed enrichment across a gene rich 200 kb region whereas H3 acetylation localizes at the transcriptional start site (TSS) of genes. We show that the DES LCR and TSS of DES are enriched with hyperacetylated domains of acetylated histone H3, with H3 lysine 4 di- and tri-methylation (H3K4me2 and me3) exhibiting a different distribution pattern across this locus. The CpG island that extends into the first intron of DES is methylation-free regardless of the gene's expression status and in non-expressing PBMCs is marked with histone H3 lysine 27 tri-methylation (H3K27me3). Overall, our results constitute the first study correlating patterns of histone modifications and underlying DNA methylation of a muscle-specific LCR and its associated downstream gene region whilst additionally placing this within a much broader genomic context. Our results clearly show that there are distinct patterns of histone H3 and H4 acetylation and H3 methylation at the DES LCR, promoter and intragenic region. In addition, the presence of H3K27me3 at the DES methylation-free CpG only in non-expressing PBMCs may serve to silence this gene in non-muscle tissues. Generally, our work demonstrates the importance of using multiple, physiologically relevant tissue types that represent different expressing/non-expressing states when investigating epigenetic marks and that underlying DNA methylation status should be correlated with histone modification patterns when studying chromatin structure.
登录
查看更多内容
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA
影响因子：
9.8
作者：
Bradbury J
通讯作者：
Bradbury J
影响因子：
7
作者：
Koch, Christoph M.;Andrews, Robert M.;Dunham, Ian
通讯作者：
Dunham, Ian
影响因子：
56.9
作者：
Hellman, Asaf;Chess, Andrew
通讯作者：
Chess, Andrew
影响因子：
64.8
作者：
Boyer, LA;Plath, K;Jaenisch, R
通讯作者：
Jaenisch, R