Long range interaction of cis-DNA elements mediated by architectural transcription factor Bach1.
BACKGROUND
A central question in vertebrate transcriptional regulation is how cis-regulatory modules, including enhancers, silencers and promoters, communicate with each other over long distances to mandate proper gene expression. In order to address this question we analysed protein/DNA interactions in the human beta-globin locus control region (LCR). One of the many proteins that are potentially implicated in LCR function is Bach1. Bach1 possesses a basic leucine zipper (bZip) domain, as well as a BTB/POZ domain that has been shown to be involved in the regulation of chromatin structure. Bach1 forms heterodimers with small Maf proteins through its leucine zipper and binds to Maf recognition elements (MARE).


RESULTS
Using atomic force microscopy we visualized large looped DNA structures between MAREs located in different regulatory elements within the human beta-globin LCR that were mediated by Bach1/MafK heterodimers. The formation of these DNA loops required the Bach1 BTB/POZ protein interaction domain. Furthermore, in transfection studies we found that Bach1 repressed the enhancer activity of the LCR in a BTB/POZ domain-dependent manner.


CONCLUSIONS
Our results suggest that Bach1 and other BTB/POZ transcription factors may represent a class of nuclear architectural proteins that mediate long range interactions between cis-regulatory elements in order to regulate gene expression.
Yoshida
C
C
Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Tokumasu
F
F
Hohmura
K I
KI
Bungert
J
J
Hayashi
N
N
Nagasawa
T
T
Engel
J D
JD
Yamamoto
M
M
Takeyasu
K
K
Igarashi
K
K
D050976:Basic-Leucine Zipper Transcription Factors; D004247:DNA / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051856:Fanconi Anemia Complementation Group Proteins; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D019901:Locus Control Region / Q000235:genetics; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics
C402243:ABTB1 protein, human; C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA