The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences

Martijn Haar; Magda Meester - Smoor; KHM (Karel) van Wely; CCMM (Claudia C. M.) Schot; MJFW (Marjolein) Janssen; B (Bart) Geverts; J Bonten; GC Grosveld; Adriaan Houtsmuller; Ellen Zwarthoff

doi:10.1371/journal.pone.0046085

The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences

Martijn Haar, Magda Meester - Smoor, KHM (Karel) van Wely, CCMM (Claudia C. M.) Schot, MJFW (Marjolein) Janssen, B (Bart) Geverts, J Bonten, GC Grosveld, Adriaan Houtsmuller, Ellen Zwarthoff

Pathology

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

29 Downloads (Pure)

Abstract

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 similar to 20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, similar to 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.

Original language	Undefined/Unknown
Journal	PLoS One (print)
Volume	7
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0046085
Publication status	Published - 2012

Research programs

EMC MM-03-24-01

Access to Document

10.1371/journal.pone.0046085

journal.pone.0046085.pdfOther version, 1.88 MB
66882.pdfFinal published version, 1.88 MB

http://hdl.handle.net/1765/66882

Cite this

@article{b5cbae8bd5c74abdb65acd8cd38f57b8,

title = "The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences",

abstract = "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 similar to 20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, similar to 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.",

author = "Martijn Haar and {Meester - Smoor}, Magda and {van Wely}, {KHM (Karel)} and Schot, {CCMM (Claudia C. M.)} and Janssen, {MJFW (Marjolein)} and Geverts, {B (Bart)} and J Bonten and GC Grosveld and Adriaan Houtsmuller and Ellen Zwarthoff",

year = "2012",

doi = "10.1371/journal.pone.0046085",

language = "Undefined/Unknown",

volume = "7",

journal = "PLoS One (print)",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences

AU - Haar, Martijn

AU - Meester - Smoor, Magda

AU - van Wely, KHM (Karel)

AU - Schot, CCMM (Claudia C. M.)

AU - Janssen, MJFW (Marjolein)

AU - Geverts, B (Bart)

AU - Bonten, J

AU - Grosveld, GC

AU - Houtsmuller, Adriaan

AU - Zwarthoff, Ellen

PY - 2012

Y1 - 2012

N2 - 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 similar to 20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, similar to 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.

AB - 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 similar to 20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, similar to 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.

U2 - 10.1371/journal.pone.0046085

DO - 10.1371/journal.pone.0046085

M3 - Article

C2 - 23049943

SN - 1932-6203

VL - 7

JO - PLoS One (print)

JF - PLoS One (print)

IS - 9

ER -