Polycomb recruitment attenuates retinoic acid–induced transcription of the bivalent NR2F1 gene

Abstract

Polycomb proteins play key roles in mediating epigenetic modifications that occur during cell differentiation. The Polycomb repressive complex 2 (PRC2) mediates the tri-methylation of histone H3 lysine 27 (H3K27me3). In this study, we identify a distinguishing feature of two classes of PRC2 target genes, represented by the Nr2F1 (Coup-TF1) and the Hoxa5 gene, respectively. Both genes are transcriptionally activated by all-trans retinoic acid (RA) and display increased levels of the permissive H3K9/K14ac and tri-methylated histone H3 lysine 4 epigenetic marks in response to RA. However, while in response to RA the PRC2 and H3K27me3 marks are greatly decreased at the Hoxa5 promoter, these marks are initially increased at the Nr2F1 promoter. Functional depletion of the essential PRC2 protein Suz12 by short hairpin RNA (shRNA) technology enhanced the RA-associated transcription of Nr2F1, Nr2F2, Meis1, Sox9 and BMP2, but had no effect on the Hoxa5, Hoxa1, Cyp26a1, Cyp26b1 and RARβ2 transcript levels in wild-type embryonic stem cells. We propose that PRC2 recruitment attenuates the RA-associated transcriptional activation of a subset of genes. Such a mechanism would permit the fine-tuning of transcriptional networks during differentiation.

An Alternative Retinoic Acid-responsive Stra6 Promoter Regulated in Response to Retinol Deficiency

“…On a molecular level, RA mediates major changes in epigenetic marks on specific target genes (33)(34)(35)(36)(37). We recently showed that Stra6 transcripts are increased by RA treatment of embryonic stem (ES) cells and that this induction depends on RAR␥ (38).…”

Novel genetic causes for cerebral visual impairment

“…44 Retinoic acid signaling induces optic vesicle and brain development and Nr2f1 and Nr2f2 transcription in mice stem cells. 45 These findings indicate that RERE is a likely candidate gene for CVI (http://www. REREgene.com).…”

Retinoic acid inhibits histone methyltransferase Whsc1 during palatogenesis

“…In neuroblastoma cells, RA induced neural maturation through RET gene transcriptional activation by increasing H3K4me3 levels at the promoter region and demethylating H3K27me3 at an enhancer region [13]. Furthermore, during RAinduced F9 cell differentiation, Nr2f1 and Hoxa5 are transcriptionally activated by RA and display increased levels of the permissive H3K9/K14ac and H3K4me3 epigenetic marks [14]. These studies suggest that RA can regulate gene expression by alteration of histone modifications in different cells.…”