An interaction proteomics survey of transcription factor binding at recurrent TERT promoter mutations.

Abstract:

:Aberrant telomerase reactivation in differentiated cells represents a major event in oncogenic transformation. Recurrent somatic mutations in the human telomerase reverse transcriptase (TERT) promoter region, predominantly localized to two nucleotide positions, are highly prevalent in many cancer types. Both mutations create novel consensus E26 transformation-specific (ETS) motifs and are associated with increased TERT expression. Here, we perform an unbiased proteome-wide survey of transcription factor binding at TERT promoter mutations in melanoma. We observe ELF1 binding at both mutations in vitro and we show that increased recruitment of GABP is enabled by the spatial architecture of native and novel ETS motifs in the TERT promoter region. We characterize the dynamics of competitive binding between ELF1 and GABP and provide evidence for ELF1 exclusion by transcriptionally active GABP. This study thus provides an important description of proteome-wide, mutation-specific binding at the recurrent, oncogenic TERT promoter mutations.

journal_name

Proteomics

journal_title

Proteomics

authors

Makowski MM,Willems E,Fang J,Choi J,Zhang T,Jansen PW,Brown KM,Vermeulen M

doi

10.1002/pmic.201500327

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

417-26

issue

3

eissn

1615-9853

issn

1615-9861

journal_volume

16

pub_type

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