Multivalent DNA binding complex generated by small Maf and Bach1 as a possible biochemical basis for beta-globin locus control region complex.
The human beta-globin locus control region (LCR) is required to properly regulate chromatin domain opening, replication timing, and globin gene activation. The LCR contains multiple NF-E2 sites (Maf recognition elements, MAREs) that allow the binding of various basic leucine zipper (bZip) proteins like p45 NF-E2, Nrf1, Nrf2, Bach1, and Bach2, in some cases as obligate heterodimers with a small Maf protein. In addition to the bZip domain, the Bach proteins bear a BTB/POZ domain, which has been implicated in the regulation of chromatin structure. We show here that Bach1 is highly expressed in hematopoietic cells and constitutes one of the two MARE-binding activities in murine erythroleukemic (MEL) cells. We further demonstrate that Bach1/MafK heterodimers interact with each other through the BTB domain, generating a multimeric and multivalent DNA binding complex. These results strongly implicate Bach1/MafK heterodimer as an architectural transcription factor that mediates interactions among multiple MAREs. Such a factor could then provide a model for assembly of the theoretical beta-globin LCR "holocomplex. " Other BTB domain proteins have already been demonstrated to be involved in remodeling chromatin, and thus this class of proteins likely promote the formation of nucleoprotein complexes required to establish the architecture of regulatory domains.
Igarashi
K
K
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tenno-dai 1-1-1, Tsukuba 305, Japan.
Hoshino
H
H
Muto
A
A
Suwabe
N
N
Nishikawa
S
S
Nakauchi
H
H
Yamamoto
M
M
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D001854:Bone Marrow Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D050981:Erythroid-Specific DNA-Binding Factors; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006410:Hematopoiesis; D006801:Humans; D050985:MafK Transcription Factor; D051379:Mice; D008810:Mice, Inbred C57BL; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins / Q000502:physiology*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D015533:Transcriptional Activation
C102108:BACH1 protein, human; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D051856:Fanconi Anemia Complementation Group Proteins; C494695:MAFK protein, human; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C494693:Nfe2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D005914:Globins