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Vol. 16, No. 1, pp. 27-32, January 1, 2002
knockdown by engineered transcription factors: exogenous PPAR2 but not PPAR1 reactivates adipogenesis
1 Department of Molecular Science and Technology, Pfizer Global
and Research Development, Ann Arbor, Michigan 48105, USA; 2 Sangamo
BioSciences Inc., Pt. Richmond, California 94804, USA
To determine functional differences between the two splice
variants of PPAR
(1 and 2), we sought to selectively repress 2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the 2-specific promoter, P2. In 3T3-L1 cells, expression of ZFP55 resulted in >50% reduction in 2 expression but had no effect on 1, whereas adipogenesis was similarly reduced by 50%. However, ZFP54 virtually abolished both 2 and 1 expression, and
completely blocked adipogenesis. Overexpression of exogenous 2 in
the ZFP54-expressing cells completely restored adipogenesis, whereas
overexpression of 1 had no effect. This finding clearly identifies a
unique role for the PPAR2 isoform.
[Key Words:
PPAR1; PPAR2; adipogenesis; zinc finger
protein]
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