Transcriptional regulation by zinc-finger proteins Sp1 and MAZ involves interactions with the same cis-elements.
Various transcription factors, such as Sp1 and MAZ, include C2H2-type zinc-finger motifs and are able to bind to GC-rich cis-elements that are distributed in the promoter regions of numerous mammalian genes. The consensus sequence of Sp1-binding sites is very similar to that of MAZ-binding sites. In fact, Sp1 and MAZ bind to the same cis-elements in the promoters of the genes for the receptor for serotonin 1A (HT1Ar), endothelial nitric-oxide synthase (eNOS), phenylethanolamine N-methyltransferase (PNMT), the receptor for parathyroid hormone (PTHr), MAZ and the major late promoter of adenovirus (AdMLP). It appears that two consecutive zinc-finger motifs of Sp1 and MAZ might be essential for the interaction of each protein with DNA. Sp1 and MAZ activated the expression of the genes for HT1Ar and PTHr, as well as AdMLP. Both Sp1 and MAZ inhibited the expression of the gene for MAZ, while expression of the gene for eNOS was enhanced by Sp1 and repressed by MAZ. These observations suggest that both Sp1 and MAZ might have dual functions in the regulation of gene expression. Our results suggest, furthermore, that histone deacetylases are involved in autorepression of the gene for MAZ, while expression of DNA methyltransferase I is associated with suppression of the expression of the gene for MAZ by Sp1. Thus, both deacetylation and methylation might be involved in the regulation of expression of individual genes, with different zinc-finger proteins binding to the same cis-elements but recruiting different proteins, such as methylases and acetylases, to the transcriptional complex.
Song
Jun
J
Gene Engineering Division, Department of Biological Systems, BioResource Center, Tsukuba Institute, RIKEN (The Institute of Physical and Chemical Research), Ibaraki 305-0074, Japan.
Ugai
Hideyo
H
Nakata-Tsutsui
Hatsumi
H
Kishikawa
Shotaro
S
Suzuki
Erika
E
Murata
Takehide
T
Yokoyama
Kazunari K
KK
D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein