Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression.

Abstract:

:COUP-TF, an orphan member of the nuclear receptor superfamily, has been proposed to play a key role in regulating organogenesis, neurogenesis, and cellular differentiation during embryonic development. Since heterodimierization is a common theme within the nuclear receptor superfamily and has been demonstrated to modulate transcriptional properties of heterodimeric partners via allosteric interactions, we have devised a strategy to examine the silencing function of COUP-TF in a heterodimeric context. We find that the intrinsic active repression function of COUP-TF is not affected by heterodimerization. Moreover, COUP-TF can transrepress the ligand-dependent activation of its heterodimeric partners without its own DNA binding site. Using receptor deletion mutants in transfection assays, we show that the region necessary for COUP-TF silencing function is not sufficient for its transrepression activity. Furthermore, our studies indicate that in addition to its active repression function, COUP-TF can repress several different types of activator-dependent transactivation. However, this active repression function of COUP-TF may be differentially regulated by some other activator(s). These studies provide new insights into the molecular mechanism(s) of COUP-TF-mediated repression.

journal_name

Mol Cell Biol

authors

Leng X,Cooney AJ,Tsai SY,Tsai MJ

doi

10.1128/mcb.16.5.2332

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

2332-40

issue

5

eissn

0270-7306

issn

1098-5549

journal_volume

16

pub_type

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