The LIM-only protein LMO4 modulates the transcriptional activity of HEN1.
The basic helix-loop-helix protein HEN1 and the LIM-only proteins LMO2 and LMO4 are expressed in neuronal cells. HEN1 was cloned by virtue of its homology to TAL1, a bHLH protein important for early hematopoiesis. Since it has been shown that TAL1 forms complex with LMO proteins in erythroid and leukemic cells we investigated the capacity of HEN1 to form complex with LMO2 and LMO4. By mammalian two-hybrid analysis, we show that HEN1 interacts with both LMO2 and LMO4. To characterize the transcriptional capacity of HEN1 alone or together with LMO2 and LMO4, we performed reporter gene assays. In comparison with the ubiquitously expressed bHLH protein E47, HEN1 is a very modest transcriptional activator and titration experiments indicate that HEN1, like TAL1, represses E47 mediated transcriptional activation. Furthermore, LMO4 but not LMO2 was able to augment this effect. Overexpression of HEN1 in hippocampal precursor cells resulted in neurite extension, which could be prevented by LMO4. Taken together, these results indicate that LMO proteins can modulate the transcriptional activity of HEN1.
Manetopoulos
Christina
C
Department of Laboratory Medicine, Division of Molecular Medicine, Lund University, University Hospital MAS, Malmö S-205 02, Sweden.
Hansson
Anders
A
Karlsson
Jenny
J
Jönsson
Jan-Ingvar
JI
Axelson
Håkan
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000378:metabolism; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C085117:LMO2 protein, human; C114905:LMO4 protein, human; C544912:TCF7L1 protein, human; C076746:NHLH1 protein, human