THE ROLE OF THE NURD COMPLEX IN GLUCOCORTICOID-ACTIVATED TRANSCRIPTION

Abstract

The glucocorticoid receptor regulates gene expression through interaction with proteins that regulate post-translational modifications. HDAC1 plays a positive role in the transcription of glucocorticoid-activated genes, yet the underlying mechanisms are unknown. Multiple complexes can contain HDAC1, one of which is the NuRD complex. NuRD’s constitution is variable between cell types due to the many homologous proteins that can compose the complex, such as HDAC1 and/or HDAC2 and its scaffold proteins: MTA1-3. The variable composition may influence NuRD complex function making it essential to characterize it in a given model system. To study whether HDAC1’s role as a transcriptional activator is mediated through the NuRD complex, the MTA scaffolds were depleted so the effects of NuRD on glucocorticoid-activated genes can be assayed. We find that HDAC1 and HDAC2 associate with NuRD in our hepatoma cell line and that MTA1 and MTA2 can be present in the same NuRD complex. Our results also show that knocking down MTA1 and MTA2 concurrently has little effect on transcription of GR target genes. Although additional studies are warranted, we currently conclude that the NuRD complex does not play a sizeable role in the regulation of glucocorticoid-activated gene transcription.