Screening of transcription factors with transcriptional initiation activity.
A majority of mammalian promoters are associated with CpG islands. CpG island promoters frequently lack common core promoter elements, such as the TATA box, and often have dispersed transcription start sites. The mechanism through which CpG island promoters are transcriptionally initiated remains unclear. We speculate that some transcription factors can direct transcription initiation by themselves. To test this hypothesis, we screened a variety of transcription factors to see whether they could initiate transcription. Most transcription factors, including specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), showed little transcriptional initiation activity. However, nuclear respiratory factor 1 (NRF-1), the basic helix-loop-helix/leucine zipper (bHLH/ZIP) family of proteins and the E-twenty six (Ets) family of proteins had strong transcriptional activity. We further demonstrated that these transcription factors initiate dispersed transcription. Our studies provide perspectives to the mechanism of transcription initiation from CpG island promoters.
Protein Science Key Laboratory of the Ministry of Education, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhanglang08@mails.tsinghua.edu.cn.
Lang
L
Zhang
Haoyue
H
Yu
Pan
P
Wang
Qingyang
Q
Ding
Zhao
Z
Wang
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018899:CpG Islands; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D016385:TATA Box; D014157:Transcription Factors / Q000378:metabolism*; D061785:Transcription Initiation, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D051265:NF-E2-Related Factor 1; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors
5′-RACE; 5′-rapid amplification of cDNA ends; AP1; BREs; C/EBP; CCAAT-enhancer-binding protein; CREB; CpG island; DCE; DPE; E-twenty six; Elf; Elk; Ets; Ets family; Ets-like factor; Ets-like protein; GA-binding protein α subunit; GABPA; IDE; Inr; MAX; MTE; MTFA; Myc-associated factor X; NF-1; NF-Y; NRF-1; PAR; POLRMT; Sp1; TATA-binding protein; TBP; TFB1M; TFE3; TFEB; TFIIB-recognition elements; Transcription initiation; UQBP; USF; activator protein 1; bHLH/ZIP; bHLH/ZIP family; bZIP; basic helix–loop–helix/leucine zipper; basic leucine zipper; c-Myc; cAMP-response element binding protein; cellular myelocytomatosis oncogene; dimethyladenosine transferase 1; downstream core element; downstream promoter element; initiator element; insulin-degrading enzyme; mitochondrial DNA-directed RNA polymerase; mitochrondrial transcription factor A; motif ten element; nuclear factor Y; nuclear respiratory factor 1; nuclear transcription factor 1; proline and acidic amino acid-rich proteins; specificity protein 1; transcription factor E3; transcription factor EB; ubiquinone binding protein; upstream stimulatory factor