Chromatin structure of the LCR in the human β-globin locus transcribing the adult δ- and β-globin genes

KLF1 stabilizes GATA-1 and TAL1 occupancy in the human β-globin locus

“…4E-G), in spite of the unaffected presence of these proteins in KLF1 knockdown MEL/ch11 cells. Exception at HS2 might be related with the strong binding of these activators that is established before transcriptional activation in MEL/ch11 cells [24]. Thus, these results showed that in the adult β-globin locus KLF1 plays a role in the occupancy of GATA-1, NF-E2 and TAL1.…”

“…To ask whether KLF1 plays a role in GATA-1 binding in the β-globin locus transcribing the human adult β-globin gene, we inhibited KLF1 expression in hybrid MEL/ch11 cells where human chromosome 11 is present and the β-globin gene is highly transcribed by chemical treatment [24]. Transduction using lentiviral shRNA decreased the KLF1 expression, but GATA-1, NF-E2 and TAL1 were expressed with modest increase (Fig.…”

“…KLF1 is detected in the LCR of human β-globin locus transcribing the embryonic and fetal globin genes or the adult globin genes in primitive erythroid cells of transgenic mice or hybrid MEL/ch11 cells, respectively [10,24]. It seems likely that KLF1 binds to the β-globin locus in human erythroid K562 cells where the fetal γ-globin genes are mainly transcribed.…”

3.4 Rational Approaches for Transgene Expression: Targeted Integration and Episomal Maintenance

“…The components LCRs commonly colocalize to sites of DNAse I hypersensitivity (HS) in the chromatin of target gene expressing cells. The most prominent activity of LCRs is their strong transcription enhancing activity, as was studied in detail in case of the human developmentally regulated β-globin locus [51]. The functional role of LCRs became evident with studies in transgenic mice where it was determined that the LCR was responsible for developmental expression of the ɛ-globin genes [52,53].…”

“…This folded structure of the LCR physically forms a loop that brings the enhancer with bound transcription factors in close proximity to the gene promoter allowing an interaction between the distant enhancer with the promoter. This interaction between promoter and enhancer allows the formation of a functional transcriptional apparatus by sharing LCR-bound coactivators and transcription factors with the basal transcription apparatus present at the promoter [51].…”