The leukemia-associated fusion protein MN1-TEL combines the transcription-activating domains of MN1 with the DNA-binding domain of the transcriptional repressor TEL. Quantitative photobleaching experiments revealed that ~20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, ~50% of the MN1-TEL fusion protein was immobile with much longer binding times than unfused MN1 and TEL. MN1-TEL immobilisation was not observed when the TEL DNA-binding domain was disrupted, suggesting that MN1-TEL stably occupies TEL recognition sequences, preventing binding of factors required for proper transcription regulation, which may contribute to leukemogenesis.

dx.doi.org/10.1371/journal.pone.0046085, hdl.handle.net/1765/66882
PLoS ONE
Department of Pathology

ter Haar, W.M, Meester-Smoor, M.A, van Wely, K.H.M, Schot, C.C.M.M, Janssen, M.J.F.W, Geverts, B, … Zwarthoff, E.C. (2012). The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences. PLoS ONE, 7(9). doi:10.1371/journal.pone.0046085