β-Catenin Primes Organizer Gene Expression by Recruiting a Histone H3 Arginine 8 Methyltransferase, Prmt2

Abstract

Summary An emerging concept in development is that transcriptional poising pre-sets patterns of gene expression in a manner that reflects a cell’s developmental potential. However, it is not known how certain loci are specified in the embryo to establish poised chromatin architecture as the developmental program unfolds. We find that, in the context of transcriptional quiescence prior to the midblastula transition in Xenopus, dorsal specification by the Wnt/β-catenin pathway is temporally uncoupled from the onset of dorsal target gene expression, and that β-catenin establishes poised chromatin architecture at target promoters. β-catenin recruits the arginine methyltransferase Prmt2 to target promoters, thereby establishing asymmetrically dimethylated H3 arginine 8 (R8). Recruitment of Prmt2 to β-catenin target genes is necessary and sufficient to establish the dorsal developmental program, indicating that Prmt2-mediated histone H3R8 methylation plays a critical role downstream of β-catenin in establishing poised chromatin architecture and marking key organizer genes for later expression.

Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition

“…zebrafish and Xenopus embryos. 5,28,29 This assay allows us to evaluate global transcriptional activity in combination with N:C ratio on an individual cell basis.…”

“…Indeed, analyses of RNA synthesis and large-scale gene expression have found zygotic gene expression in Drosophila, Xenopus and zebrafish well before the MBT. 1,[4][5][6]45,46 Additionally, gene expression profiling data from haploid and diploid Drosophila embryos suggest more complex regulation of zygotic transcription, with distinct subsets of zygotic transcripts that depend either on time or on the N:C ratio. 1 Our studies also provide insight into cell cycle remodeling at the MBT.…”

“…With a few exceptions [1][2][3][4][5][6][7] transcription of the vast majority of zygotic genes starts at the MBT. How the onset of ZGA is regulated is a long-standing question, and several models have been proposed.…”

The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation

“…Recent evidence suggests that alterations in DNA methylation and histone modifications around the time of MBT are important for zygotic gene activation [47,[87][88][89][90]. Similarly, β-catenin recruits the arginine methyltransferase Prmt2 to target promoters, thereby establishing poised chromatin architecture and priming organizer gene expression [91]. Whether the transcriptional activity of maternal β-catenin is controlled by internal self-regulating protein modifications remains unknown.…”

An Overview of Gene Regulation by Wnt/β‐Catenin Signaling

“…These include MLL1/2 (H3K4me3), protein arginine methyltransferase 2 (PMRT2, H3R8me), SET8 (H3K20me), CARM1 (H3R17me2), and DOTL1/DOT1 (H3K79me3) (Blythe et al, 2010;Chen et al, 2010;Li et al, 2011b;Mahmoudi et al, 2010;Mohan et al, 2010;Ou et al, 2011;Sierra et al, 2006). It is not clear how consistently chromatin modifications occur among different Wnt targets, for example, for some targets, there is no change in histone acetylation upon Wnt signaling (Blythe et al, 2010;Wohrle, Wallmen, and Hecht, 2007). In contrast, a microarray study in HEK293T cells demonstrated that most genes that are activated by Wnt3a treatment required DOTL1 for this regulation (Mahmoudi et al, 2010).…”