Cloning MafF by recognition site screening with the NFE2 tandem repeat of HS2: analysis of its role in globin and GCSl genes regulation.
The erythroid-specific enhancer within hypersensitivity site 2 (HS2) of the human beta-globin locus control region is required for high level globin gene expression. We used an oligonucleotide of the NF-E2 tandem repeat, within HS2, as recognition site probe to screen a K562 cDNA library for interacting transcription factors. A 2.3 kb full length cDNA encoding the b-zip transcription factor MafF was isolated. MafF can form both homodimers and high affinity heterodimers with Nrf1, Nrf2 and Nf-E2, three members of the CNC-bZip family. Despite obvious structural similarities with the other small Maf proteins, MafF differs in its tissue distribution and its inability to repress transcription when overexpressed as homodimer. In fact, in different cell lines and on different promoters (gamma-globin, beta-globin and glutamylcysteine synthetase genes) the MafF homodimers do not appreciably affect transcription of target promoters, whereas MafF/CNC member heterodimers act as weak transcriptional activators. Even though MafF was cloned using probes derived from the globin LCR, it is in the context of the GCSl promoter and in combination with Jun that MafF shows a rather distinct and specific regulatory role. These observations suggest that a complex network of small Maf and CNC-AP1 protein interactions might be involved in regulating transcription in diverse tissues or developmental stages.
Marini
M Giuseppina
MG
Istituto di Neurogenetica e Neurofarmacologia, CNR, Cagliari 09121, Italy.
Asunis
Isadora
I
Chan
Kaimin
K
Chan
Jefferson Y
JY
Kan
Yuet W
YW
Porcu
Loredana
L
Cao
Antonio
A
Moi
Paolo
P
D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D019281:Dimerization; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D051260:MafF Transcription Factor; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020218:Response Elements; D020080:Tandem Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C484147:MAFF protein, human; D051260:MafF Transcription Factor; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; C429222:goblet cell silencer inhibitor; D005914:Globins