AI Article Synopsis

  • The β-globin gene expression in mammals is regulated by several elements, including promoters and a locus control region (LCR), but the exact sequences needed for this regulation remain unclear.
  • Researchers performed deletions in the murine β-globin locus and discovered that removing the β2-globin gene promoter does not impact other genes' expression or chromatin structure, indicating that competition for LCR activity may not exist.
  • Additionally, they identified a new enhancer 3' of the β2-globin gene, but deleting it had no effect on gene expression or chromatin structure, underscoring the challenge in determining the functions of enhancers based on chromatin landscape or functional tests.

Article Abstract

In mammals, the complex tissue- and developmental-specific expression of genes within the β-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regulation of chromatin structure and gene expression within the cluster is not fully defined. To further elucidate regulation of the adult β-globin genes, we investigate the effects of two deletions engineered within the endogenous murine β-globin locus. First, we find that deletion of the β2-globin gene promoter, while eliminating β2-globin gene expression, results in no additional effects on chromatin structure or gene expression within the cluster. Notably, our observations are not consistent with competition among the β-globin genes for LCR activity. Second, we characterize a novel enhancer located 3' of the β2-globin gene, but find that deletion of this sequence has no effect whatsoever on gene expression or chromatin structure. This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin "landscape" or even by functional assays.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015891PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092947PLOS

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