Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood.
Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood.
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DOI：
10.2217/epi.15.104
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发表时间：
2016-01
期刊：
影响因子：
3.8
通讯作者：
Ehrlich M
中科院分区：
文献类型：
--
作者：
Buckley L;Lacey M;Ehrlich M
识别 DMPK 附近的表观遗传标记（与强直性肌营养不良，DM1 有关），有助于解释其表达的组织特异性差异。在 DMPK 及其侧翼基因（DMWD、SIX5、BHMG1 和 RSPH6A）中，我们分析了来自成肌细胞、肌管、骨骼肌、心脏和 30 个非肌肉样本的许多表观遗传和转录谱。在 DMPK 基因附近，观察到肌肉相关 DNA 高甲基化和低甲基化、增强子染色质和 CTCF 结合。肌源性 DMPK 高甲基化与高表达和替代启动子使用减少相关。 BHMG1 和 RSPH6A 的睾丸/精子低甲基化与睾丸特异性表达相关。在 DMPK 内 DM1 连接的 CTG 重复序列附近发现了 G-四链体 (G4) 基序和精子特异性低甲基化。 DMPK 和邻近基因的组织特异性表观遗传特征有助于调节其表达。 DMPK DNA 和 RNA 中的 G4 基序可能与 DM1 病理学有关。
Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression. At DMPK and its flanking genes (DMWD, SIX5, BHMG1 and RSPH6A), we analyzed many epigenetic and transcription profiles from myoblasts, myotubes, skeletal muscle, heart and 30 nonmuscle samples. In the DMPK gene neighborhood, muscle-associated DNA hypermethylation and hypomethylation, enhancer chromatin, and CTCF binding were seen. Myogenic DMPK hypermethylation correlated with high expression and decreased alternative promoter usage. Testis/sperm hypomethylation of BHMG1 and RSPH6A was associated with testis-specific expression. G-quadruplex (G4) motifs and sperm-specific hypomethylation were found near the DM1-linked CTG repeats within DMPK. Tissue-specific epigenetic features in DMPK and neighboring genes help regulate its expression. G4 motifs in DMPK DNA and RNA might contribute to DM1 pathology.