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Series GSE234155 Query DataSets for GSE234155
Status Public on Jun 07, 2023
Title Chromatin Accessibility Mapping of Primary Erythroid Cell Populations Leads to Identification and Validation of NFIX As a Novel Fetal Hemoglobin Repressor
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Human genetics has validated de-repression of fetal gamma globin (HBG) in adult erythroblasts as a powerful therapeutic paradigm in diseases involving defective adult beta globin (HBB)1. To identify factors involved in the switch from HBG to HBB expression, we performed Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq)2 on sorted erythroid lineage cells derived from bone marrow (BM) or cord blood (CB), representing adult and fetal states, respectively. BM to CB cell ATAC-seq profile comparisons revealed genome-wide enrichment of NFI DNA binding motifs and increased NFIX promoter chromatin accessibility, suggesting that NFIX may repress HBG. NFIX knockdown in BM cells increased HBG mRNA and fetal hemoglobin (HbF) protein levels, coincident with increased chromatin accessibility and decreased DNA methylation at the HBG promoter. Conversely, overexpression of NFIX in CB cells reduced HbF levels. Identification and validation of NFIX as a new target for HbF activation has implications in the development of therapeutics for hemoglobinopathies.
Overall design Global transcriptional analysis of 1) Primary bone marrow derived erythroblasts and cord blood derived eyrthroblasts across erythrocyte differention; and 2) Primary bone marrow derived erythroblasts transduced with NFIX shRNA or a non-targeting control.
Contributor(s) Chaand M, Fiore C, Johnston B, D'Ippolito A, Moon DH, Carulli JP, Shearstone JR
Citation(s) 37316562
Submission date Jun 05, 2023
Last update date Sep 08, 2023
Contact name Nisha Rajagopal
Phone 6507202183
Organization name Syros Pharmaceuticals
Street address 1069 Liberty Square Road
City Boxborough
State/province MA
ZIP/Postal code 01719
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (38)
GSM7449941 BM_Population1_Donor1_RNAseq_biorep1
GSM7449942 BM_Population2_Donor1_RNAseq_biorep1
GSM7449943 BM_Population3_Donor1_RNAseq_biorep1
BioProject PRJNA980210

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Supplementary file Size Download File type/resource
GSE234155_bm_nfix_shrna_kd_rnaseq_reads.txt.gz 1.1 Mb (ftp)(http) TXT
GSE234155_cb_and_bm_rnaseq_reads.txt.gz 1.3 Mb (ftp)(http) TXT
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