强直性肌营养不良相关DMPK基因邻域的表观遗传学
Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood.
作者信息
Buckley Lauren, Lacey Michelle, Ehrlich Melanie
机构信息
Human Genetics Program, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Tulane Cancer Center & Department of Mathematics, Tulane University, New Orleans, LA 70112, USA.
出版信息
Epigenomics. 2016 Jan;8(1):13-31. doi: 10.2217/epi.15.104. Epub 2016 Jan 12.
AIM
Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression.
MATERIALS & METHODS: 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.
RESULTS
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.
CONCLUSION
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.
目的
确定强直性肌营养不良蛋白激酶（DMPK，与强直性肌营养不良症1型[DM1]相关）附近的表观遗传标记，以帮助解释其表达中的组织特异性差异。
材料与方法
在DMPK及其侧翼基因（DMWD、SIX5、BHMG1和RSPH6A）处，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。
结果
在DMPK基因附近，观察到与肌肉相关的DNA高甲基化和低甲基化、增强子染色质以及CTCF结合。成肌DMPK高甲基化与高表达相关，并减少了替代启动子的使用。BHMG1和RSPH6A在睾丸/精子中的低甲基化与睾丸特异性表达相关。在DMPK内与DM1相关的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。
结论
DMPK及其邻近基因中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基序可能导致DM1病理。
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