Structural highlights
Function
[PRD14_MOUSE] Transcription factor that has both positive and negative roles on transcription. Plays a role in cellular pluripotency (By similarity). Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression.[1]
Publication Abstract from PubMed
Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. We generated two monobodies, synthetic binding proteins, targeting the Prdm14 SET domain and demonstrate their utility, respectively, in facilitating crystallization and structure determination of the Prdm14-Mtgr1 complex, or as genetically encoded inhibitor of the Prdm14-Mtgr1 interaction. Structure-guided point mutants and the monobody abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression and provides renewable reagents for studying and controlling Prdm14 functions.
ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation.,Nady N, Gupta A, Ma Z, Swigut T, Koide A, Koide S, Wysocka J Elife. 2015 Nov 2;4. pii: e10150. doi: 10.7554/eLife.10150. PMID:26523391[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yamaji M, Seki Y, Kurimoto K, Yabuta Y, Yuasa M, Shigeta M, Yamanaka K, Ohinata Y, Saitou M. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet. 2008 Aug;40(8):1016-22. doi: 10.1038/ng.186. Epub 2008 Jul 11. PMID:18622394 doi:http://dx.doi.org/10.1038/ng.186
- ↑ Nady N, Gupta A, Ma Z, Swigut T, Koide A, Koide S, Wysocka J. ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation. Elife. 2015 Nov 2;4. pii: e10150. doi: 10.7554/eLife.10150. PMID:26523391 doi:http://dx.doi.org/10.7554/eLife.10150
