The LRF/ZBTB7A transcription factor is a BCL11A-independent repressor of fetal hemoglobin
Transcriptomics Dataset
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General Information
AccessionGSE74977
TitleThe LRF/ZBTB7A transcription factor is a BCL11A-independent repressor of fetal hemoglobin
DescriptionHemoglobinopathies, including sickle cell disease and _-thalassemia, are global public health concerns. Induction of fetal-type hemoglobin (HbF) is a promising means to treat these disorders; however, precisely how HbF expression is silenced in adult erythroid cells is not fully understood. Here, we show that the LRF/ZBTB7A transcription factor is a potent repressor of HbF production. LRF inactivation derepresses embryonic/fetal _-globin expression in mouse and human adult erythroid cells. We employed genome-wide analysis of the transcriptome, chromatin accessibility and LRF occupancy sites, and demonstrate that LRF occupies the _-globin loci and maintains nucleosome density necessary for _-globin silencing. LRF confers its repressive activity through a unique NuRD repressor complex independent of BCL11A. Strikingly, human erythroid lines lacking both LRF and BCL11A exhibited almost a complete switch in expression from adult- to fetal-type globin, suggesting that these two factors cumulatively represent the near entirety of _-globin repressive activity in adult erythroid cells.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74977
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset

Dataset Accession
Tool Name

Interactive heatmap visualization of RNA-seq dataset GSE74977
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
Interactive heatmap visualization of RNA-seq dataset GSE74977
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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