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PU.1 is a major transcriptional activator of the tumour suppressor gene LIMD1
Author(s) -
Foxler Daniel E.,
James Victoria,
Shelton Samuel J.,
de A. Vallim Thomas Q.,
Shaw Peter E.,
Sharp Tyson V.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.03.013
Subject(s) - gene silencing , transcription factor , activator (genetics) , gene , transcription (linguistics) , promoter , microrna , biology , gene expression , cancer research , genetics , philosophy , linguistics
LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG in childhood acute lymphoblastic leukaemia. Mechanistically, LIMD1 interacts with pRB, repressing E2F‐driven transcription as well as being a critical component of microRNA‐mediated gene silencing. In this study we show a CpG island within the LIMD1 promoter contains a conserved binding motif for the transcription factor PU.1. Mutation of the PU.1 consensus reduced promoter driven transcription by 90%. ChIP and EMSA analysis demonstrated that PU.1 specifically binds to the LIMD1 promoter. siRNA depletion of PU.1 significantly reduced endogenous LIMD1 expression, demonstrating that PU.1 is a major transcriptional activator of LIMD1.