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Publication : Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci.

First Author  Pope NJ Year  2010
Journal  Nucleic Acids Res Volume  38
Issue  7 Pages  2190-200
PubMed ID  20047963 Mgi Jnum  J:173151
Mgi Id  MGI:5009784 Doi  10.1093/nar/gkp1159
Citation  Pope NJ, et al. (2010) Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci. Nucleic Acids Res 38(7):2190-200
abstractText  The critical regulator of hematopoiesis GATA-1 recruits diverse coregulators to chromatin, which mediate transcriptional activation and repression. These coregulators include the cell-type-specific multi-zinc finger protein Friend of GATA-1 (FOG-1), the histone acetyltransferase CREB binding protein (CBP), and the key component of the Mediator complex Med1. While FOG-1 is an established GATA-1 coregulator, the importance of interactions between GATA-1 and other coregulators is poorly understood. Furthermore, whether GATA-1 utilizes multiple coregulators at all loci, or if certain coregulators are dedicated to specific loci is unknown. We compared the capacity of GATA-1 to recruit and utilize FOG-1 and Med1 at activated and repressed target genes. Similar to FOG-1, GATA-1 recruited Med1 to activated genes, and the kinetics of FOG-1 and Med1 recruitment were similar. GATA-1 recruited Med1 in Fog1(-/-) cells, indicating that GATA-1-mediated Med1 recruitment is FOG-1-independent. In contrast to FOG-1, GATA-1 evicted Med1 during transcriptional repression. Whereas knocking-down FOG-1 had catastrophic effects on GATA-1-mediated activation and repression, knocking-down Med1 modestly impaired GATA-1 activity only at select loci. These results illustrate both similarities and differences between GATA-1-mediated recruitment of FOG-1 and Med1 to chromatin, with a fundamental difference being the quantitatively greater requirement for FOG-1.
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