Transcriptomics,Genomics

Dataset Information

298

The LRF/ZBTB7A transcription factor is a BCL11A-independent repressor of fetal hemoglobin


ABSTRACT: Hemoglobinopathies, 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. RNA-seq, LRF ChIP-seq and ATAC-seq assays were used to investigtae LRF binding, effect of LRF depletion on transcription and chromatin landscape in mouse and human cells.

ORGANISM(S): Musculus  

SUBMITTER: Peter V Kharchenko   Takahiro Maeda  Peter Kharchenko 

PROVIDER: E-GEOD-74977 | ArrayExpress | 2016-01-15

SECONDARY ACCESSION(S): SRP066151GSE74977PRJNA302116

REPOSITORIES: GEO, ArrayExpress, ENA

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