Hi Chloe

I don't work on GR specifically but in transcription generally so I may be able to help if you are looking for basic level information.

GR has many isoforms created through alternative splicing and as you see from the first exon, alternative transcriptional start sites. The promoter region covers a large area from 2-3 kb upstream and including regulatory elements within the gene body itself. The choice of start site is regulated by different mechanisms that will be specific to tissue or signal or development etc. This means that the promoter of each specific isoform will depend on a complex recruitment/ activation of transcriptional initiation proteins that may be restricted to a particular condition or cell type.

If you search Pubmed for GR and promoter there will be many publications suggesting a range of activators and repressors and their relative isoforms.

Each isoform will translate into a slightly different protein that may be unique to a certain cell type. Not all isoforms will be expressed in all cells. So one receptor will be one isoform. However, GR is a dimer and may, in theory, be composed of two different isoforms that may alter the function.

I would hazard a guess that, as most other proteins, the regulation of expression of each isoform of GR is far from being completely understood.

Take a look at this to see the positions of regulatory elements etc alongside the list of mRNA isoforms. And this is not an exhaustive search, nor is it describing a wide range of cells/tissues, or conditions.

https://genome-euro.ucsc.edu/cgi-bin/hgTracks?db=hg19&position=chr5%3A142531737-142909013&hgsid=198198775_qWMBBA9FOHS6mt7yau2gAJFLRvzJ

Ask away if you are still unsure about this

many thanks Amanda, you've been a great help, much appreciated

I've only just seen this........ My lab have done most of the work on the human GR gene structure, particularly the 5' end. The papers you need to read are:

Jonathan D Turner, Claude P Muller (2005) Structure of the glucocorticoid receptor (NR3C1) gene 5' untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol 35: 2. 283-292 Oct.

Jonathan D Turner, Andrea B Schote, Joana A Macedo, Laetitia P L Pelascini, Claude P Muller (2006) Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage? Biochem Pharmacol 72: 11. 1529-1537 Nov.

Jonathan D Turner, Simone R Alt, Lei Cao, Sara Vernocchi, Slavena Trifonova, Nadia Battello, Claude P Muller (2010) Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochem Pharmacol 80: 12. 1860-1868 December.

Lei Cao-Lei, Salomon Carlos Leija, Robert Kumsta, Stefan Wüst, Jobst Meyer, Jonathan D Turner, Claude P Muller (2011) Transcriptional control of the human glucocorticoid receptor: Identification and analysis of alternative promoter regions Human Genetics 129: 5. 533-43 May.

Jonathan D Turner, Sara Vernocchi, Stephanie Schmitz, Claude P Muller (In press) Role of the 5'-untranslated regions in post-transcriptional regulation of the human Glucocorticoid Receptor BBA Gene Regulatory Mechanisms.(In Press)

Most of the papers can be obtained from here or from http://publicationslist.org/jonathan.d.turner . Don't hesitate to mail me jonathan.turner AT crp-sante.lu (with the obvious change!) if you need reprints, or have any questions about the GR!

Jon

Dear Jonathan,

Thank you so much for getting back to me. I am going to sink my teeth into these papers now, which I am sure will help with my understanding of the GR and it's gene. If I have any questions, I will be in touch.

Many thanks and kind regards,

Chloe