Supplementary Figure 2 - Endometrial stromal cells - Genomic annotation of GATA2 and PGR ChIPseq
2020-04-09T19:57:41Z (GMT) by
Cistromic analysis revealed similar genome-wide binding of GATA2 to promoter regions in both Veh and IVD-treated cells.
Supplementary dataset supporting manuscript currently under review.
Abstract: The transcription factor GATA2 is important for endometrial stromal cell decidualization in early pregnancy. Progesterone receptor (PGR) is also critical during decidualization but its interaction with GATA2 in regulating genes and pathways necessary for decidualization in human endometrium are unclear. RNA-sequencing (RNA-seq) was performed to compare gene expression profiles (n=3) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) using an antibody against GATA2 (n=2) was performed to examine binding to target genes in human endometrial stromal cells undergoing in vitro decidualization (IVD including estrogen, progestin and cAMP analogue) or vehicle treatment. We identified 1232 differentially expressed genes (DEGs) in IVD vs. vehicle. GATA2 cistrome in IVD-treated cells was enriched with motifs for GATA, ATF, and JUN, and gene ontology analysis of GATA2 cistrome revealed pathways that regulate cholesterol storage, p38 MAPK and the c-Jun N-terminal kinase cascades. Integration of RNA-seq and ChIP-seq data revealed that the PGR motif is highly enriched at GATA2 binding regions surrounding upregulated genes in IVD-treated cells. The integration of a mined public PGR cistrome in IVD-treated human endometrial cells with our GATA2 cistrome showed that GATA2 binding was significantly enhanced at PGR-binding regions in IVD vs. vehicle. Interrogating two separate ChIP-seq datasets together with RNA-seq revealed integration of GATA2 and PGR action to co-regulate biologic processes during decidualization of human endometrial stromal cells, specifically via WNT activation and stem cell differentiation pathways. These findings reveal the key pathways that are co-activated by GATA2 and PGR that may be therapeutic targets for supporting implantation and early pregnancy.