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. In the TAL1 knockdown cells, the γ-globin transcription was reduced to 35% and chromatin looping of the (G)γ-globin gene with the LCR was disrupted with decreased occupancy of the complex member Ldb1 and LMO2 in the locus. However, GATA-1 binding, DNase I hypersensitive site formation and several histone modifications were largely maintained across the β-globin locus. In addition, overexpression of TAL1 increased the γ-globin transcription and increased interaction frequency between the (G)γ-globin gene and LCR. These results indicate that TAL1 plays a critical role in chromatin loop formation between the γ-globin genes and LCR, which is a critical step for the transcription of the γ-globin genes.
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea and Laboratory of Cellular and Developmental Biology, NIDDK, NIH, Bethesda, MD 20892, USA.
Won Ju
WJ
Yun
Yea Woon
YW
Kim
Yujin
Y
Kang
Jungbae
J
Lee
Ann
A
Dean
AeRi
A
Kim
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002843:Chromatin / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D060588:LIM Domain Proteins / Q000378:metabolism; D019901:Locus Control Region; D050983:NF-E2 Transcription Factor / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D055544:beta-Globins / Q000235:genetics*; D055545:gamma-Globins / Q000096:biosynthesis / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D006657:Histones; D060588:LIM Domain Proteins; D050983:NF-E2 Transcription Factor; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D055544:beta-Globins; D055545:gamma-Globins; C486312:LDB1 protein, human; C085117:LMO2 protein, human; C067143:TAL1 protein, human