Distinct Ldb1/NLI complexes orchestrate gamma-globin repression and reactivation through ETO2 in human adult erythroid cells

作者：Kiefer Christine M; Lee Jongjoo; Hou Chunhui; Dale Ryan K; Lee Y Terry; Meier Emily R; Miller Jeffrey L; Dean Ann^*

来源：Blood, 2011, 118(23): 6200-6208.

DOI：10.1182/blood-2011-06-363101

The Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction between the beta-globin locus control region (LCR) and gene in adult mouse erythroid cells, but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the beta-globin locus in human erythroid cells. In addition to the LCR, we found robust NLI complex occupancy at a site downstream of the (A)gamma-globin gene within sequences of BGL3, an intergenic RNA transcript. In cells primarily transcribing beta-globin, BGL3 is not transcribed and BGL3 sequences are occupied by NLI core complex members, together with corepressor ETO2 and by gamma-globin repressor BCL11A. The LCR and beta-globin gene establish proximity in these cells. In contrast, when gamma-globin transcription is reactivated in these cells, ETO2 participation in the NLI complex at BGL3 is diminished, as is BCL11A occupancy, and both BGL3 and gamma-globin are transcribed. In these cells, proximity between the BGL3/gamma-globin region and the LCR is established. We conclude that alternative NLI complexes mediate gamma-globin transcription or silencing through long-range LCR interactions involving an intergenic site of non-coding RNA transcription and that ETO2 is critical to this process. (Blood. 2011;118(23):6200-6208)

• 出版日期2011-12-1