The interaction of ETV6 (TEL) and TIP60 requires a functional histone acetyltransferase domain in TIP60.
The ets-family transcription factor ETV6 (TEL) has been shown to be the target of a large number of balanced chromosomal translocations in various hematological malignancies and in some soft tissue tumors. Furthermore, ETV6 is essential for hematopoietic stem cell function. We identified ETV6 interacting proteins using the yeast two hybrid system. One of these proteins is the HIV Tat interacting protein (TIP60), a histone acetyltransferase (HAT) containing the highly conserved MYST domain. TIP60 functions as a corepressor of ETV6 in reporter gene assays. Fluorescently tagged ETV6 and TIP60 colocalize in the nucleus and an increase in nuclear localization of ETV6 was seen when TIP60 was cotransfected. ETV6 interacts with TIP60 through a 63 amino acids region located in the central domain of ETV6 between the pointed and the ets domain. The ETV6 interacting region of TIP60 mapped to the C2HC zinc finger of the TIP60 MYST domain. The interaction of TIP60 with full length ETV6 required an intact acetyltransferase domain of TIP60. Interestingly, the MYST domains of MOZ and MORF were also able to interact with portions of ETV6. These observations suggest that MYST domain HATs regulate ETV6 transcriptional activity and may therefore play critical roles in leukemogenesis and possibly in normal hematopoietic development.
Putnik
Jasmina
J
Institute of Human Genetics, Heinrich-Düker-Weg 12, 37037 Göttingen, Germany.
Zhang
Chang-Dong
CD
Archangelo
Leticia Fröhlich
LF
Tizazu
Belay
B
Bartels
Sigrun
S
Kickstein
Michael
M
Greif
Philipp A
PA
Bohlander
Stefan K
SK
D000595:Amino Acid Sequence; D000818:Animals; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D000074443:Lysine Acetyltransferase 5; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D013347:Subcellular Fractions; D020798:Two-Hybrid System Techniques; D000097764:ETS Translocation Variant 6 Protein
D051548:Histone Acetyltransferases; D006877:Hydroxamic Acids; D000074443:Lysine Acetyltransferase 5; D019278:Matrix Metalloproteinase 3; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C012589:trichostatin A; C098489:KAT5 protein, human