Transcriptional activation by TLX1/HOX11 involves Gro/TLE corepressors.
The role of Groucho/transducin-like Enhancer of split (Gro/TLE) family members as corepressors of transcription is well documented. TLX1 is a homeodomain transcription factor involved in splenogenesis and neuron formation, and its aberrant expression gives rise to T-cell acute lymphoblastic leukemia. We demonstrate by glutathione-S-transferase pull-down assays, in vivo biotinylation tagging and confocal laser microscopy that TLX1 interacts with TLE1 via an Eh1-like motif. Paradoxically, we found that this motif is essential for optimal transcriptional activation of two TLX1 target genes, Aldh1a1 and Fhl1. Using a well characterized target of the Hairy/Enhancer of split 1 (HES1).TLE1 repressor complex, the ASCL1 gene, we show that TLX1 counteraction of ASCL1 repression by HES1 in SK-N-BE(2) neuroblastoma cells is associated with dismissal of TLE1 from the ASCL1 promoter and requires the Eh1-like motif for maximal effect. Collectively, these results indicate that TLX1-mediated target gene activation can occur in part via derepression strategies involving Gro/TLE corepressors.
Riz
Irene
I
Department of Anatomy and Regenerative Biology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA.
Lee
Hyo Jung
HJ
Baxter
Kristin K
KK
Behnam
Reza
R
Hawley
Teresa S
TS
Hawley
Robert G
RG
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D020816:Amino Acid Motifs; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D060588:LIM Domain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050697:Retinal Dehydrogenase; D015533:Transcriptional Activation
D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D050697:Retinal Dehydrogenase; C065500:ASCL1 protein, human; C101149:FHL1 protein, human; C499043:TLE1 protein, human; C071250:TLX1 protein, human; C510223:ALDH1A1 protein, human