Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex.
Human Bex2 (brain expressed X-linked, hBex2) is highly expressed in the embryonic brain, but its function remains unknown. We have identified that LMO2, a LIM-domain containing transcriptional factor, specifically interacts with hBex2 but not with mouse Bex1 and Bex2. The interaction was confirmed both by pull-down with GST-hBex2 and by coimmunoprecipitation assays in vivo. Using electrophoretic mobility shift assay, we have demonstrated the physical interaction of hBex2 and LMO2 as part of a DNA-binding protein complex. We have also shown that hBex2 can enhance the transcriptional activity of LMO2 in vivo. Furthermore, using mammalian two-hybrid analysis, we have identified a neuronal bHLH protein, NSCL2, as a novel binding partner for LMO2. We then showed that LMO2 could up-regulate NSCL2-dependent transcriptional activity, and hBex2 augmented this effect. Thus, hBex2 may act as a specific regulator during embryonic development by modulating the transcriptional activity of a novel E-box sequence-binding complex that contains hBex2, LMO2, NSCL2 and LDB1.
Han
Chunyu
C
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Chinese National Human Genome Center, Beijing, People's Republic of China.
Liu
Hao
H
Liu
Jin
J
Yin
Kang
K
Xie
Yi
Y
Shen
Xiao
X
Wang
Yong
Y
Yuan
Jiangang
J
Qiang
Boqing
B
Liu
Yong-Jian
YJ
Peng
Xiaozhong
X
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins; D016415:Sequence Alignment; D014157:Transcription Factors; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008667:Metalloproteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C469586:BEX1 protein, human; C530662:BEX2 protein, human; C486312:LDB1 protein, human; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; C076747:NHLH2 protein, human