Loss of E2F7 expression is an early event in squamous differentiation and causes derepression of the key differentiation activator Sp1

Hazar-Rethinam, Mehlika, Cameron, Sarina R., Dahler, Alison L., Endo-Munoz, Liliana B., Smith, Louise, Rickwood, Danny and Saunders, Nicholas A. (2011) Loss of E2F7 expression is an early event in squamous differentiation and causes derepression of the key differentiation activator Sp1. Journal of Investigative Dermatology, 131 5: 1077-1084. doi:10.1038/jid.2010.430


Author Hazar-Rethinam, Mehlika
Cameron, Sarina R.
Dahler, Alison L.
Endo-Munoz, Liliana B.
Smith, Louise
Rickwood, Danny
Saunders, Nicholas A.
Title Loss of E2F7 expression is an early event in squamous differentiation and causes derepression of the key differentiation activator Sp1
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
1523-1747
Publication date 2011-05
Sub-type Article (original research)
DOI 10.1038/jid.2010.430
Volume 131
Issue 5
Start page 1077
End page 1084
Total pages 8
Place of publication London, United Kingdom
Publisher Nature
Collection year 2012
Language eng
Abstract Squamous differentiation is controlled by key transcription factors such as Sp1 and E2F. We have previously shown that E2F1 can suppress transcription of the differentiation-specific gene, transglutaminase type 1 (TG1), by an indirect mechanism mediated by Sp1. Transient transfection of E2F1-E2F6 indicated that E2F-mediated reduction of Sp1 transcription was not responsible for E2F-mediated suppression of squamous differentiation. However, we found that E2F4 and E2F7, but not E2Fs 1, 2, 3, 5, or 6, could suppress the activation of the Sp1 promoter in differentiated keratinocytes (KCs). E2F4-mediated suppression could not be antagonized by E2Fs 1, 2, 3, 5, or 6 and was localized to a region of the human Sp1 promoter spanning-139 to +35 bp. Chromatin immunoprecipitation analysis, as well as transient overexpression and short hairpin RNA knockdown experiments indicate that E2F7 binds to a unique binding site located between-139 and-119 bp of the Sp1 promoter, and knockdown of E2F7 in proliferating KCs leads to a derepression of Sp1 expression and the induction of TG1. In contrast, E2F4 knockdown in proliferating KCs did not alter Sp1 expression. These data indicate that loss of E2F7 during the initiation of differentiation leads to the derepression of Sp1 and subsequent transcription of differentiation-specific genes such as TG1.
Keyword Human epidermal-keratinocytes
Cell carcinoma
Transcription factors
Epithelial-cells
Gene-expression
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Thu, 20 Oct 2011, 11:36:38 EST by Nicholas Saunders on behalf of School of Biomedical Sciences