| Experiment Id | GSE142226 | Name | Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin accessibility and looping (RNA-Seq) |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-12-03 |
| description | ETO2 functions as a transcription repressor and is required for the embryonic erythropoiesis and the hemoglobin switch. To gain insight into ETO2 regulatory function during human erythropoiesis, we performed RNA-seq for WT and ETO2 KO K562 cells and found that up-regulated genes upon ETO2 loss in human cells included many markers of mature erythroid cells EPB42, ALAS2, GYPA and SLC25a37. Notably, the alpha-globin genes (HBA1, HBA2 and HBZ) and embryonic and fetal beta-globin genes (HBE1, HBG1, and HBG2) were significantly increased after deletion of ETO2. By contrast, deletion of ETO2 down-regulated the transcription factor genes (ETS1, KLF8 and SOX6) which play a negative role in globin gene expression and hemoglobin synthesis. To further explore different domain function of ETO2, we have analyzed our RNA-seq data from domain deletion cell lines compared to the cell line expressing wild type ETO2. Generally, 702 genes were found to co-regulated by three domain function of ETO2. Interestingly, the regulation of fetal globin genes, erythroid regulator (SOX5) as well as epigenetic factor (HDAC7) is required by three domain function of ETO2. During mouse embryonic erythropoiesis, our FACS-sorted and normal RNA-seq data in E14.5 fetal liver cells indicated that eto2 promoted a critical developmental transition and played an important role in globin switch from embryonic to adult beta-globin transcription since its function is essential for key regulators (PU.1, BCL11A and ZBTB7A) and globin genes (Hbb-y and Hba-x) regulation. RNA-seq was performed between human erythroleukemia K562 control cells and ETO2 KO cells in order to identify the differentially expressed genes. RNA-seq was performed in WT control, KO control, rescued ETO2 full length (FL), rescued ETO2 full length without domain TAF110 (D1), rescued ETO2 full length without domain HHR (D2) and rescued ETO2 full length without domain ZF (D4) K562 cells to identify the differentially expressed genes and genes regulated by different functional domains. RNA-seq was performed using FACS-sorted and total embryonic day 14.5 (E14.5) fetal liver cells between control and Eto2 knockout mice to identify the differentially expressed genes which are essential for mouse development and embryonic erythropoiesis. |
