The hypersensitive sites of the murine β-globin locus control region act independently to affect nuclear localization and transcriptional elongation.

Publication Type:

Journal Article

Source:

Blood, Volume 119, Issue 16, p.3820-3827 (2012)

Keywords:

2012, Basic Sciences Division, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Flow Cytometry Core Facility, Mar 2012, March 2012, Proteomics Core Facility, Shared Resources

Abstract:

The β-globin locus control region (LCR) is necessary for high-level β-globin gene transcription and differentiation-dependent relocation of the β-globin locus from the nuclear periphery to the central nucleoplasm and to foci of hyper-phosphorylated Pol II "transcription factories" (TFys). To determine the contribution of individual LCR DNaseI hypersensitive sites (HSs) to transcription and nuclear location, we compared β-globin gene activity and location in erythroid cells derived from mice with deletions of individual HSs, deletions of two HSs and deletion of the whole LCR. We find that each HS has a similar spectrum of activities, albeit to different degrees. Each HS acts as an independent module to activate expression in an additive manner, and this correlates with relocation away from the nuclear periphery. In contrast, HSs have redundant activities with respect to association with TFys and the probability that an allele is actively transcribed, as measured by primary RNA transcript FISH. The limiting effect on RNA levels occurs after β-globin genes associate with TFys, at which time HSs contribute to the amount of RNA arising from each burst of transcription by stimulating transcriptional elongation.