Epigenomic Reorganization of the Clustered Hox Genes in Embryonic Stem Cells Induced by Retinoic Acid

RARγ is Essential for Retinoic Acid Induced Chromatin Remodeling and Transcriptional Activation in Embryonic Stem Cells

“…We detected binding of RXRa at the Cyp26a1 promoter, our positive control (supplementary material Fig. S1), consistent with our previous studies indicating that Cyp26a1 is a direct RA target gene (Kashyap et al, 2011). Consequently, the Meis1 proximal promoter region appears to be devoid of functional RAREs.…”

“…We showed that the polycomb protein Suz12 interacts with RARc in the absence of RA in ES cells and that this interaction is abrogated upon RA addition; however this interaction may not be by direct binding and could be bridged through association with other transcriptional regulators, such as co-repressors (Amat and Gudas, 2011). Importantly, by using the RARc 2/2 ES cells we have shown that the lack of RARc does not interfere with the basal association of the PcG mediated H3K27me3 mark at the Hoxa and Hoxb clusters and other RA targets, such as Cyp26a1 (Kashyap et al, 2011) and Meis1 (Fig. 3F).…”

“…1C; supplementary material Table S6B, Table S7B). In accord with previous studies, transcript levels of Zfp42 (Rex1), a stem cell marker, were ES cells were generated as described previously (Kashyap et al, 2011 Table S4A). Thus, RARc is implicated in regulating this group of genes and our results also suggest that other RARs, i.e.…”

“…ES cells have a stable genome and possess the capacity to differentiate into the three germ layers, thus making them an excellent cell culture system to study RA mediated differentiation in vitro (Gudas and Wagner, 2011;Soprano et al, 2007). We previously reported that RARc null ES cells do not differentiate into parietal endoderm, an epithelial cell type, in response to RA (Kashyap et al, 2011).…”

Retinoid Signaling is a Context-Dependent Regulator of Embryonic Stem Cells

“…), resulting transcription of primary target genes; 2) Induces expression of transcription factors (Hox, Cdx, etc) and other signaling molecules, resulting transcription of secondary target genes. Regulation of non-coding RNAs may serve as additional level of retinoid action (Rossi, D'Urso et al 2010); 3) Alters interactions with proteins involved in epigenetic regulation (Kashyap, Gudas et al 2011). Furthermore, there are proteins that bind at or near RAREs resulting a more complex mechanism of retinoid action (for review, see (Gudas and Wagner 2011).…”