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DNA binding and dimerisation properties of the transcription factor COUP-TF II

Butler, Alison Jane; (1995) DNA binding and dimerisation properties of the transcription factor COUP-TF II. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The chicken ovalbumin upstream transcription factors (COUP-TF I and II) are members of the nuclear receptor family. These proteins have no identified ligand and can repress the transcriptional activity of a number of other nuclear receptors including the receptors for retinoic acid (RAR and RXR), thyroid hormone (TR) and oestrogen (ER). Analysis of COUP-TF protein revealed that its expression can be regulated by both retinoic acid and oestrogen indicating that COUP-TF mediated repression in vivo may be subject to hormonal controls. COUP-TF II was shown to bind DNA in vitro either as a homodimer or as heterodimer with RXRa or TR. To establish whether COUP-TF II could form homodimers and heterodimers in vivo the dimerisation properties of this orphan receptor were investigated in transfected cells using a two hybrid assay. In conditions where COUP-TF II homodimers and RXRa/RARa heterodimers were formed heterodimers between COUP-TF II and RXRa were not detected. Moreover, no interaction between COUP-TF II and RXRa could be detected on DNA in intact cells. Similarly, COUP-TF II homodimers and RXRa/TR heterodimers were favoured over COUP-TF II/TR heterodimers. These results suggest that the formation of functionally inactive heterodimers is unlikely to represent a general mechanism by which COUP-TF represses the transcriptional activity of nuclear receptors and a model is favoured in which repression is mediated by COUP-TF homodimers competing for DNA binding. In support of this model COUP-TF II homodimers recognised a variety of nuclear receptor response elements that differed in the spacing and orientation of the half site motifs in contrast to the more restricted binding of other members of the family. Multiple and independent dimerisation interfaces were identified within COUP-TF II which may impart the flexibility of binding required for the degenerate response element specificity displayed by the homodimer.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: DNA binding and dimerisation properties of the transcription factor COUP-TF II
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10098920
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