Changes in DNA methylation hallmark alterations in chromatin accessibility and gene expression for eye lens differentiation.
Changes in DNA methylation hallmark alterations in chromatin accessibility and gene expression for eye lens differentiation.
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DNA甲基化的变化是眼透镜分化中染色质可及性和基因表达改变的标志。
DOI：
10.1186/s13072-022-00440-z
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发表时间：
2022-03-05
影响因子：
3.9
通讯作者：
Kantorow M
中科院分区：
文献类型：
--
作者：
Disatham J;Brennan L;Jiao X;Ma Z;Hejtmancik JF;Kantorow M
胞嘧啶甲基化(MCG)是众所周知的基因表达调节因子，但其对细胞分化的要求尚未完全阐明。一个研究得很好的细胞分化模型系统是眼晶状体，它由单一的前层上皮细胞组成，这些上皮细胞横向迁移并分化为纤维细胞的核心。在这里，我们探索了眼晶状体上皮细胞分化为纤维细胞过程中MCG甲基化、染色质可及性和基因表达之间的全基因组关系。全基因组测序鉴定了7621个基因组座位，显示晶状体上皮细胞和纤维细胞之间的MCG水平存在显著差异。MCG水平的变化与晶状体纤维或晶状体上皮细胞中优先表达的1285个基因的分化状态特异性表达呈负相关(Pearson相关性r = −=0.37，p <； 1 × 10-42)。MCG水平与转座酶可及测序法(ATAC-SEQ)确定的染色质可及性呈负相关(Pearson相关性r = −=0.86，p <； 1 × 10-300)。与上皮细胞相比，纤维细胞中DNA甲基化、染色质可及性和基因表达水平发生改变的许多基因与晶状体纤维细胞结构、动态平衡和透明度有关。这些蛋白包括晶状体蛋白(CRYBA4、CRYBB1、CRYGN、CRYBB2)、晶状体珠状细丝蛋白(BFSP1、BFSP2)、转录因子(HSF4、SOX2、HIF1a)和Notch信号通路成员(NOTCH1、NOTCH2、HEY1、HES5)。对DNA甲基化中显示细胞类型特异性改变的区域的分析表明，包括HIF1a、SOX2和MAF转录因子家族在内的多种已知在晶状体细胞分化中起关键作用的转录因子的共同序列过度表达。总的来说，这些结果将DNA甲基化与控制染色质可及性和眼睛晶状体分化所需的基因表达变化联系在一起。研究结果还表明，DNA甲基化在转录因子的调控中发挥了作用，这些转录因子以前被认为是晶状体细胞分化的重要因素。网上版载有补充材料，可在10.1186/s13072-022-00440-z查阅。
Methylation at cytosines (mCG) is a well-known regulator of gene expression, but its requirements for cellular differentiation have yet to be fully elucidated. A well-studied cellular differentiation model system is the eye lens, consisting of a single anterior layer of epithelial cells that migrate laterally and differentiate into a core of fiber cells. Here, we explore the genome-wide relationships between mCG methylation, chromatin accessibility and gene expression during differentiation of eye lens epithelial cells into fiber cells. Whole genome bisulfite sequencing identified 7621 genomic loci exhibiting significant differences in mCG levels between lens epithelial and fiber cells. Changes in mCG levels were inversely correlated with the differentiation state-specific expression of 1285 genes preferentially expressed in either lens fiber or lens epithelial cells (Pearson correlation r = − 0.37, p < 1 × 10–42). mCG levels were inversely correlated with chromatin accessibility determined by assay for transposase-accessible sequencing (ATAC-seq) (Pearson correlation r = − 0.86, p < 1 × 10–300). Many of the genes exhibiting altered regions of DNA methylation, chromatin accessibility and gene expression levels in fiber cells relative to epithelial cells are associated with lens fiber cell structure, homeostasis and transparency. These include lens crystallins (CRYBA4, CRYBB1, CRYGN, CRYBB2), lens beaded filament proteins (BFSP1, BFSP2), transcription factors (HSF4, SOX2, HIF1A), and Notch signaling pathway members (NOTCH1, NOTCH2, HEY1, HES5). Analysis of regions exhibiting cell-type specific alterations in DNA methylation revealed an overrepresentation of consensus sequences of multiple transcription factors known to play key roles in lens cell differentiation including HIF1A, SOX2, and the MAF family of transcription factors. Collectively, these results link DNA methylation with control of chromatin accessibility and gene expression changes required for eye lens differentiation. The results also point to a role for DNA methylation in the regulation of transcription factors previously identified to be important for lens cell differentiation. The online version contains supplementary material available at 10.1186/s13072-022-00440-z.
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影响因子：
3.4
作者：
Brennan LA;McGreal-Estrada R;Logan CM;Cvekl A;Menko AS;Kantorow M
通讯作者：
Kantorow M
影响因子：
5.5
作者：
Anand D;Al Saai S;Shrestha SK;Barnum CE;Chuma S;Lachke SA
通讯作者：
Lachke SA
影响因子：
10.5
作者：
Cantù C;Zimmerli D;Hausmann G;Valenta T;Moor A;Aguet M;Basler K
通讯作者：
Basler K
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
2.7
作者：
Burnett JB;Lupu FI;Eggenschwiler JT
通讯作者：
Eggenschwiler JT