Characterization of NERF, a novel transcription factor related to the Ets factor ELF-1.
We have cloned the gene for a novel Ets-related transcription factor, new Ets-related factor (NERF), from human spleen, fetal liver, and brain. Comparison of the deduced amino acid sequence of NERF with those of other members of the Ets family reveals that the level of homology to ELF-1, which is involved in the regulation of several T- and B-cell-specific genes, is highest. Homologies are clustered in the putative DNA binding domain in the middle of the protein, a basic domain just upstream of this domain, and several shorter stretches of homology towards the amino terminus. The presence of two predominant NERF transcripts in various fetal and adult human tissues is due to at least three alternative splice products, NERF-1a, NERF-1b, and NERF-2, which differ in their amino termini and their expression in different tissues. Only NERF-2 and ELF-1, and not NERF-1a and NERF-1b, function as transcriptional activators of the lyn and blk gene promoters, although all isoforms of NERF bind with affinities similar to those of ELF-1 to a variety of Ets binding sites in, among others, the blk, lck, lyn, mb-1, and immunoglobulin H genes and are expressed at similar levels. Since NERF and ELF-1 are coexpressed in B and T cells, both might be involved in the regulation of the same genes.
Oettgen
P
P
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Akbarali
Y
Y
Boltax
J
J
Best
J
J
Kunsch
C
C
Libermann
T A
TA
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005326:Fetal Proteins / Q000302:isolation & purification; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins; D009928:Organ Specificity; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000235:genetics
D004268:DNA-Binding Proteins; C512897:ELF1 protein, human; C512896:Elf1 protein, mouse; D005326:Fetal Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C101003:ELF2 protein, human; C082599:protein-tyrosine kinase p55(blk); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases