Huntingtin Facilitates Polycomb Repressive Complex 2

DSpace/Manakin Repository

Huntingtin Facilitates Polycomb Repressive Complex 2

Citable link to this page


Title: Huntingtin Facilitates Polycomb Repressive Complex 2
Author: Woda, Juliana M.; Song, Ji-Joon; Lloret, Alejandro; Abeyrathne, Priyanka D.; Gregory, Gillian; Lee, Jong-Min; Conlon, Ronald A.; Seong, Ihn Sik; Woo, Caroline; Wheeler, Vanessa Chantal; Walz, Thomas; Kingston, Robert Edward; Gusella, James Francis; MacDonald, Marcy Elizabeth

Note: Order does not necessarily reflect citation order of authors.

Citation: Seong, Ihn Sik, Juliana M. Woda, Ji-Joon Song, Alejandro Lloret, Priyanka D. Abeyrathne, Caroline J. Woo, Gillian Gregory, et al. 2010. Huntingtin facilitates polycomb repressive complex 2. Human Molecular Genetics 19(4): 573-583.
Full Text & Related Files:
Abstract: Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat α-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large α-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure–function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in \(Hdh^{Q111}\) EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's α-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region.
Published Version: doi:10.1093/hmg/ddp524
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search