+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A carboxyl-terminal extension of the zinc finger domain contributes to the specificity and polarity of peroxisome proliferator-activated receptor DNA binding

, : A carboxyl-terminal extension of the zinc finger domain contributes to the specificity and polarity of peroxisome proliferator-activated receptor DNA binding. Journal of Biological Chemistry 273(43): 27988-27997

Heterodimers of the peroxisome proliferator-activated receptors (PPAR) and the retinoid X receptors (RXR) recognize response elements (PPREs) that exhibit the consensus sequence 5'-A(A/T)CT(A/G)GGNCAAAG/G/T)TCA-3'. The consensus PPRE includes both a 5'-extension and a direct repeat (DR1) comprised of two canonical core recognition sequences (underlined) for nuclear receptor zinc fingers separated by a single nucleotide spacer. The extended binding site recognized by PPARs is very similar to sites that bind monomers of the nuclear receptors Rev-ErbA and ROR suggesting that the latter could bind to PPREs and affect gene transcription. However, Rev-ErbA and ROR bind weakly to naturally occurring PPREs relative to the consensus binding site, and significant effects on PPARalpha transactivation of a CYP4A6-Z reporter were not observed. In contrast, PPAR/RXR heterodimers bind to a DR2 element containing the conserved 5'-extended sequence that is recognized by dimers of RORalpha or Rev-ErbA. PPARalpha/RXRalpha positively regulate transcription from this element, and co-expression of Rev-ErhA blocks this effect. The nuclear receptors NGFI-B and ROR utilize a carboxyl-terminal extension (CTE) of the zinc finger DNA binding domain in their interactions with the 5'-extension of a single zinc finger-binding site. DNA binding domains (DBD) of PPARs alpha, delta, and gamma that contain the zinc finger motif and a CTE display binding to core recognition sequences that is dependent on the 5'-extended sequence found in PPREs. Unlike DBDs of other nuclear receptors that form heterodimers with RXR, the PPAR-DBDs did not exhibit cooperative binding with the DBD of RXR and exhibit the opposite polarity for binding to the direct repeat motif. In contrast to the corresponding DBD of RXR, the PPAR-DBDs bind as monomers to a single extended binding site as well as to the consensus PPRE. A chimera binding the zinc finger domain of RXRalpha to the CTE from PPARalpha bound to a single extended binding site indicating a functional role for the CTE of PPARs in extended binding site recognition.


PMID: 9774413

DOI: 10.1074/jbc.273.43.27988

Other references

Shrestha, N.R.; Pilgrim, T.; Basnet, A.; Karki, P.; Cook, S.; Urban, P., 2013: Percutaneous coronary intervention for acute coronary syndromes in eastern Nepal: a preliminary report. Swiss Medical Weekly 143: W13737-W13737

Lv, Z.; Wang, J.; Deng, L.; Chen, G., 2009: Preparation and Characterization of Covalently Binding of Rat Anti-human IgG Monolayer on Thiol-Modified Gold Surface. The 16-mercaptohexadecanoic acid (MHA) film and rat anti-human IgG protein monolayer were fabricated on gold substrates using self-assembled monolayer (SAM) method. The surface properties of the bare gold substrate, the MHA film and the protein m...

Robertson, N.J.; Mccarthy, L.S.; Hamilton, P.A.; Moss, A.L.H., 1996: Nasal deformities resulting from flow driver continuous positive airway pressure. Over a period of six months, seven cases were documented of trauma to the nose as a result of flow driver continuous positive airway pressure in babies of very low birthweight (VLBW). There was a complication rate of 20% in the babies who required...

Liu DanHong; Cui ChangYuan; M.Z.ongYu, 2000: A new species of Helina R.- D. from Heilongjiang, China (Diptera: Muscidae). A new species of Helina, Helina raoheensis sp. nov. is presented. It is similar to H. bohemani but differs in the colouring of its legs.

Besson, J.; Graff, M., 1997: Emergency medicine for the practitioner: suicidal crisis. Revue Medicale de la Suisse Romande 117(4): 299-300

Courade, G., 1983: Setting up state agroindustrial empires since independence in Cameroon: a rural development and/or national development policy?. Over a 20 year development period state agroindustrial complexes have absorbed a considerable amount of Cameroon's development and agricultural resources. The peasant farming sector has meanwhile been suppressed, purchasing power has fallen,...

Iyer, S.; Rele, S.; Grasa, G.; Nolan, S.; Chaikof, E.L., 2003: Synthesis of a hyaluronan neoglycopolymer by ring-opening metathesis polymerization. A hyaluronan (HA)-derived disaccharide was synthesized bearing an n-pentenyl spacer arm, which facilitated disaccharide derivatization with a norbornene template. Subsequent ring opening metathesis polymerization of the monomer produced an HA-mime...

Webb, P.; Sangal, S., 1991: Sedentary daily expenditure: a base for estimating individual energy requirements. As a base for estimating individual energy requirements, we propose using the energy expenditure of a sedentary day with regular meals and sleep at night. Ninety-five 24- h measurements of sedentary daily expenditure (SDE) by direct calorimetry on...

Ashton, J.R., 2001: Public health service needs to be independent. Bmj 321(7274): 1473-1473

Niggli V., 1990: Effect of protein kinase activation and inhibition on the association of alpha actinin with the neutrophil cytoskeleton. Experientia (Basel) 46(ABSTR): A18