Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci.
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.
Pope
Nathaniel J
NJ
University of Wisconsin School of Medicine and Public Health, Wisconsin Institute for Medical Research, Madison, WI 53705, USA.
Bresnick
Emery H
EH
D000818:Animals; D002460:Cell Line; D004900:Erythroblasts / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056426:Genetic Loci; D007700:Kinetics; D056913:Mediator Complex Subunit 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse