Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3334K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tadokoro, Y. Articles by Nakauchi, H. Search for Related Content PubMed PubMed Citation Articles by Tadokoro, Y. Articles by Nakauchi, H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Stem Cells Social Bookmarking                      What's this?

¹ Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
² Laboratory for Mammalian Epigenetic Studies, Center for Developmental Biology, Institute of Physical and Chemical Research (RIKEN), Kobe 650-0047, Japan
³ Novartis Institutes for Biomedical Research, Cambridge, MA 02139

CORRESPONDENCE Hiromitsu Nakauchi: nakauchi{at}ims.u-tokyo.ac.jp

DNA methylation is an epigenetic modification essential for development. The DNA methyltransferases Dnmt3a and Dnmt3b execute de novo DNA methylation in gastrulating embryos and differentiating germline cells. It has been assumed that these enzymes generally play a role in regulating cell differentiation. To test this hypothesis, we examined the role of Dnmt3a and Dnmt3b in adult stem cells. CD34^–/low, c-Kit⁺, Sca-1⁺, lineage marker^– (CD34^– KSL) cells, a fraction of mouse bone marrow cells highly enriched in hematopoietic stem cells (HSCs), expressed both Dnmt3a and Dnmt3b. Using retroviral Cre gene transduction, we conditionally disrupted Dnmt3a, Dnmt3b, or both Dnmt3a and Dnmt3b (Dnmt3a/Dnmt3b) in CD34^– KSL cells purified from mice in which the functional domains of these genes are flanked by two loxP sites. We found that Dnmt3a and Dnmt3b function as de novo DNA methyltransferases during differentiation of hematopoietic cells. Unexpectedly, in vitro colony assays and in vivo transplantation assays showed that both myeloid and lymphoid lineage differentiation potentials were maintained in Dnmt3a-, Dnmt3b-, and Dnmt3a/Dnmt3b-deficient HSCs. However, Dnmt3a/Dnmt3b-deficient HSCs, but not Dnmt3a- or Dnmt3b-deficient HSCs, were incapable of long-term reconstitution in transplantation assays. These findings establish a critical role for DNA methylation by Dnmt3a and Dnmt3b in HSC self-renewal.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Takashima, S., Takehashi, M., Lee, J., Chuma, S., Okano, M., Hata, K., Suetake, I., Nakatsuji, N., Miyoshi, H., Tajima, S., Tanaka, Y., Toyokuni, S., Sasaki, H., Kanatsu-Shinohara, M., Shinohara, T. (2009). Abnormal DNA Methyltransferase Expression in Mouse Germline Stem Cells Results in Spermatogenic Defects. Biol. Reprod. 81: 155-164 [Abstract] [Full Text]  
• Tadokoro, Y., Ema, H., Okano, M., Li, E., Nakauchi, H. (2007). De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. JCB 177: i3-i3 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS