کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039610 1073070 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs
چکیده انگلیسی


• Tet enzymes maintain telomere length
• Tet enzymes maintain chromosomal stability of ESCs
• Dnmt3b and 5hmC are involved in Tet-signaling-mediated telomere maintenance
• Excessive Zscan4 and Dnmt3b lead to heterogeneous telomere elongation and loss

SummaryTen-eleven translocation (Tet) family proteins convert 5-methylcytosine to 5-hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs) depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3β inhibitors), which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels.

Graphical AbstractFigure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 15, Issue 8, 24 May 2016, Pages 1809–1821
نویسندگان
, , , , , , , , , , , , , , , , , , ,