Biased, Non-equivalent Gene-Proximal and -Distal Binding Motifs of Orphan Nuclear Receptor TR4 in Primary Human Erythroid Cells

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Sequential genome-wide binding studies investigated by deep sequencing (ChIP-seq) represent a powerful tool for investigating the temporal sequence of gene activation and repression events that take place as cells differentiate. Here, we report the binding of an “orphan” nuclear receptor (one for which no ligand has been identified) to its cognate genomic regulatory sites and perform the functional analysis to validate its downstream targets as precursor cells differentiate from very early human hematopoietic progenitors into red blood cells. We discovered that when this receptor is bound at gene proximal promoters, it recognizes a different DNA sequence than when it binds to more distant regulatory sites (enhancers and silencers). Since this receptor can either activate or repress specific target genes, the data suggest the intriguing possibility that the two different modes of DNA recognition may reflect association of the receptor with different partner molecules when regulating gene expression from proximal or distal sequences.

Vyšlo v časopise: Biased, Non-equivalent Gene-Proximal and -Distal Binding Motifs of Orphan Nuclear Receptor TR4 in Primary Human Erythroid Cells. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004339
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004339

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