Transcription of the mitochondrial citrate carrier gene: identification of a silencer and its binding protein ZNF224.
In the last few years, we have been functionally characterizing the promoter of the human mitochondrial citrate carrier (CIC). In this study we show that CIC silencer activity extends over 26 bp (-595/-569), which specifically bind a protein present in HepG2 cell nuclear extracts. This transcription factor was purified by DNA affinity and identified as ZNF224. Overexpression of ZNF224 decreases LUC transgene activity in cells transfected with a construct containing the CIC silencer region, whereas ZNF224 silencing activates reporter transcription in cells transfected with the same construct. Moreover, overexpression and silencing of ZNF224 diminishes and enhances, respectively, CIC transcript and protein levels. Finally, ZNF224 is abundantly expressed in fetal tissues contrary to CIC. It is suggested that CIC transcriptional repression by ZNF224 explains, at least in part, the low expression of CIC in fetal tissues in which fatty acid synthesis is low.
Iacobazzi
Vito
V
Department of Pharmaco-Biology, University of Bari, Bari, Italy.
Infantino
Vittoria
V
Convertini
Paolo
P
Vozza
Angelo
A
Agrimi
Gennaro
G
Palmieri
Ferdinando
F
D027321:Anion Transport Proteins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D027361:Organic Anion Transporters; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D037941:Silencer Elements, Transcriptional; D014158:Transcription, Genetic
D027321:Anion Transport Proteins; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; D012097:Repressor Proteins; C532592:Slc25a1 protein, human; C470003:ZNF224 protein, human