DNMT3B inhibits the re-expression of genes associated with induced pluripotency

Experimental Cell Research
Patompon WongtrakoongatePeter W Andrews

Abstract

DNMT3B is a de novo DNA methyltransferase that is highly expressed in mouse and human embryonic stem (ES) cells and has been shown to be essential for differentiation of mouse ES cells toward different lineages. In the present study, we found that DNMT3B is rapidly down-regulated in human ES cells during retinoic acid (RA)-induced differentiation compared with DNMT3A2, which is also highly expressed in ES cells. Silencing of DNMT3B in human ES cells by an inducible shRNAi system leads to a reduction of clonal ability of the stem cells, while expression of OCT4 and NANOG is unchanged. By contrast, the germline-specific genes VASA and SCP3 and the surface antigen BE12 are down regulated following DNMT3B knockdown. Upon retinoic acid-induced differentiation, we found that depletion of DNMT3B leads to a decrease in expression of the surface antigen A2B5 and of neural tube-associated genes PAX7 and BRN3A. Consistent with its importance in stem cell differentiation, we observed that silencing of DNMT3B facilitates the generation of cells that bear the hallmarks of pluripotency. Our findings suggest a role of DNMT3B in controlling the differentiation of human ES cells and in the generation of iPS cells.

References

Nov 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D Solter, B B Knowles
Oct 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·G S EisenbarthM Nirenberg
Nov 6, 1998·Science·J A ThomsonJ M Jones
Apr 18, 2000·Human Molecular Genetics·D M Juriloff, M J Harris
Apr 5, 2002·Nature·Ina RheeBert Vogelstein
May 17, 2002·The Journal of Biological Chemistry·Normand BeaulieuA Robert MacLeod
May 30, 2002·Journal of Anatomy·Jonathan S DraperPeter W Andrews
Nov 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jamie M SpergerJames A Thomson
Dec 3, 2003·Blood·Carla E Blanco-BetancourtClaudine Schiff
Sep 15, 2005·Human Molecular Genetics·Tariq EnverPeter W Andrews
Apr 4, 2006·Molecular and Cellular Biology·Haijiang LinRudolf Jaenisch
Jul 11, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Akiko TsumuraMasaki Okano
Jun 19, 2007·Nature Biotechnology·UNKNOWN International Stem Cell InitiativeWeidong Zhang
May 30, 2008·Nature·Tarjei S MikkelsenAlexander Meissner
Jun 6, 2009·Cell Stem Cell·Jennifer Nichols, Austin Smith
Jul 10, 2009·Nature·Alexandre Gaspar-MaiaMiguel Ramalho-Santos
Jul 22, 2009·Molecular and Cellular Biology·Shinwu JeongPeter A Jones
Oct 15, 2009·Nature Biotechnology·Elayne M ChanThorsten M Schlaeger
Mar 18, 2010·Stem Cells·Stuart AveryPeter W Andrews
May 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yasuhiro SekiMakoto Asashima
Jun 17, 2010·Cell·Nishant SinghalHans R Schöler
Oct 7, 2010·Nucleic Acids Research·Katsunobu KashiwagiYasufumi Kaneda
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·Alexandre Gaspar-MaiaMiguel Ramalho-Santos
Jun 10, 2011·International Journal of Andrology·A WrightN J Harrison

❮ Previous
Next ❯

Citations

Jan 18, 2016·Biomaterials·Chen-Shuang LiChia Soo
Aug 3, 2014·Biochimica Et Biophysica Acta·Rujapope SutiwisesakPatompon Wongtrakoongate
Aug 28, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Tianchi ChenEduardo D Sontag
Jun 13, 2017·The Journal of Reproduction and Development·Fujia WuLei An
Jun 21, 2020·Developmental Biology·Siba Shanak, Volkhard Helms
May 30, 2021·Briefings in Functional Genomics·Brenna S McCauley, Weiwei Dang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.