Epigenetic regulations of the Sall genes in embryonic and trophoblast stem cells and involvement of non‐coding RNA

• DOI: 10.1096/fasebj.24.1_supplement.713.5
• Publication Date: 2021-06-15T18:16:36Z
• Authors: Jun Ohgane; Katsuyoshi Kumagai; Takeshi Takamatsu; Shintaro Yagi; Satoshi Tanaka; Kunio Shiota
• Keywords: 0301 basic medicine; 03 medical and health sciences

Epigenetics including DNA methylation is involved in gene silencing and fundamental to embryonic development in mammals. Genome‐wide DNA methylation analyses have indicated that there are numerous tissue‐dependent and differentially methylated regions (T‐DMRs). Mammals have four Spalt‐like genes (Sall1–4), which encode C2H2 type transcription factors and are indispensable for normal embryonic development. We found that all the Sall family genes contained T‐DMRs that were hypomethylated in embryonic stem (ES) cells but hypermethylated in trophoblast stem (TS) cells, together with specific histone methylation patterns and promoter‐associated antisense non‐coding RNAs (ASncRNAs). Among them, Sall4 is required for self‐renewal of ES cells and prevents differentiation into trophoblast lineages. We identified an ASncRNA overlapping with the Sall4 promoter T‐DMR, and the Sall4 ASncRNA was expressed in ES cells but barely detected in TS cells. The expression pattern of the Sall4 ASncRNA was similar to that of sense Sall4 mRNA and inversely correlated with the DNA methylation pattern. In conclusion, we have found T‐DMRs in all the Sall genes, and promoter‐associated antisense RNA is likely involved in epigenetic regulation of Sall family genes.This work was supported by KAKENHI (21248039) from MEXT, Japan.