Identification of the Coiled-Coil Domain as an Essential Methyl-CpG-Binding Domain Protein 3 Element for Preserving Lineage Commitment Potential of Embryonic Stem Cells

Stem Cells
Masataka HirasakiAkihiko Okuda

Abstract

Embryonic stem cells (ESCs) exhibit two salient features beneficial for regenerative medicine: unlimited self-renewal and pluripotency. Methyl-CpG-binding domain protein 3 (Mbd3), a scaffolding component of the nucleosome remodeling deacetylase complex, is a specific regulator of pluripotency, as ESCs lacking Mbd3 are defective for lineage commitment potential but retain normal self-renewal properties. However, functional similarities and dissimilarities among the three Mbd3 isoforms (a, b, and c) have not been intensively explored. Herein, we demonstrated that Mbd3c, which lacks an entire portion of the MBD domain, exerted equivalent activity for counteracting the defective lineage commitment potential of Mbd3-knockout ESCs. Our analyses also revealed that the coiled-coil domain common to all three MBD3 isoforms, but not the MBD domain, plays a crucial role in this activity. Mechanistically, our data demonstrate that the activity of the coiled-coil domain is exerted, at least in part, through recruitment of polycomb repressive complex 2 to a subset of genes linked to development and organogenesis, thus establishing stable transcriptional repression. Stem Cells 2018;36:1355-1367.

References

Oct 17, 1998·Molecular and Cellular Biology·B Hendrich, A Bird
Jan 24, 2006·Molecular and Cellular Biology·Xavier Le GuezennecHendrik G Stunnenberg
Feb 8, 2006·Nature Cell Biology·Keisuke KajiBrian Hendrich
Jul 8, 2011·Nature Reviews. Cancer·Anne Y Lai, Paul A Wade
May 9, 2012·Cell Stem Cell·Guang Hu, Paul A Wade
Jan 5, 2013·Science·Le CongFeng Zhang
May 20, 2014·Cell Stem Cell·Rodrigo L dos SantosJosé C R Silva
Dec 3, 2014·Cell Stem Cell·Pedro J BatistaHoward Y Chang
Dec 30, 2014·Frontiers in Genetics·Roberta Menafra, Hendrik G Stunnenberg
Mar 31, 2016·Nature Communications·Ayumu SuzukiAkihiko Okuda

❮ Previous
Next ❯

Citations

Dec 24, 2019·Journal of Molecular Biology·Cathia RauschM Cristina Cardoso

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

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.