A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members

Xiaoqin Xu, Mark Bieda, Victor X. Jin, Alina Rabinovich, Mathew J. Oberley, Roland Green, Peggy J. Farnham

Research output: Contribution to journalArticle

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Abstract

Using ChIP-chip assays (employing ENCODE arrays and core promoter arrays), we examined the binding patterns of three members of the E2F family in five cell types. We determined that most E2F1, E2F4, and E2F6 binding sites are located within 2 kb of a transcription start site, in both normal and tumor cells. In fact, the majority of promoters that are active (as defined by TAF1 or POLR2A binding) in GM06990 B lymphocytes and Ntera2 carcinoma cells were also bound by an E2F. This very close relationship between E2F binding sites and binding sites for general transcription factors in both normal and tumor cells suggests that a chromatin-bound E2F may be a signpost for active transcription initiation complexes. In general, we found that several E2Fs bind to a given promoter and that there is only modest cell type specificity of the E2F family. Thus, it is difficult to assess the role of any particular E2F in transcriptional regulation, due to extreme redundancy of target promoters. However, Ntera2 carcinoma cells were exceptional in that a large set of promoters were bound by E2F6, but not by E2F1 or E2F4. It has been proposed that E2F6 contributes to gene silencing by recruiting enzymes involved in methylating histone H3. To test this hypothesis, we created Ntera2 cell lines harboring shRNAs to E2F6. We found that reduction of E2F6 only induced minimal alteration of the transcriptome of Ntera2 transcriptome. Our results support the concept of functional redundancy in the E2F family and suggest that E2F6 is not critical for histone methylation.

Original languageEnglish (US)
Pages (from-to)1550-1561
Number of pages12
JournalGenome Research
Volume17
Issue number11
DOIs
StatePublished - Nov 2007

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Neoplasms
Binding Sites
Transcriptome
Histones
General Transcription Factors
Carcinoma
Transcription Initiation Site
Gene Silencing
Methylation
Chromatin
B-Lymphocytes
Cell Line
Enzymes

ASJC Scopus subject areas

  • Genetics

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A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. / Xu, Xiaoqin; Bieda, Mark; Jin, Victor X.; Rabinovich, Alina; Oberley, Mathew J.; Green, Roland; Farnham, Peggy J.

In: Genome Research, Vol. 17, No. 11, 11.2007, p. 1550-1561.

Research output: Contribution to journalArticle

Xu, Xiaoqin ; Bieda, Mark ; Jin, Victor X. ; Rabinovich, Alina ; Oberley, Mathew J. ; Green, Roland ; Farnham, Peggy J. / A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. In: Genome Research. 2007 ; Vol. 17, No. 11. pp. 1550-1561.
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