Erythroid specific activator GATA-1-dependent interactions between CTCF sites around the β-globin locus.

CTCF sites (binding motifs for CCCTC-binding factor, an insulator protein) are located considerable distances apart on genomes but are closely positioned in organized chromatin. The close positioning of CTCF sites is often cell type or tissue specific. Here we analyzed chromatin organization in eight CTCF sites around the β-globin locus by 3C assay and explored the roles of erythroid specific transcription activator GATA-1 and KLF1 in it.

Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the human adult β-globin locus.

The β-like globin genes are developmental stage specifically transcribed in erythroid cells. The transcription of the β-like globin genes requires erythroid specific activators such as GATA-1, NF-E2, TAL1 and KLF1. However, the roles of these activators have not fully elucidated in transcription of the human adult β-globin gene.

The hematopoietic regulator TAL1 is required for chromatin looping between the β-globin LCR and human γ-globin genes to activate transcription.

TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL1 in transcription activation of the human γ-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hairpin RNA, compromising its association in the β-globin locus.