Structural insights into the DNA-binding specificity of E2F family transcription factors

Morgunova, Ekaterina; Yin, Yimeng; Jolma, Arttu; Dave, Kashyap; Schmierer, Bernhard; Попов, А. Н.; Eremina, Nadejda; Nilsson, Lennart; Taipale, Jussi

doi:10.1038/ncomms10050

Cited by 58 publications

(46 citation statements)

References 42 publications

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“…The distribution of feature importance ("Maximum," "Minimum," and "ΔMinimum") observed in our model mainly ranges ±350 bp around the binding sites, which may be related to the previously reported neighboring TF binding peaks. Furthermore, the prevalent symmetric feature importance patterns can be associated with the symmetric homodimeric or heterodimeric TF-TF-DNA complex structures, including HNF (Chi et al 2002;Yan et al 2013), E2F (Morgunova et al 2015), and MAX (Nair and Burley 2006) TF families.…”

Section: Distant Chromatin Architecture and Tf-tf Interactions Determmentioning

confidence: 99%

Anchor: trans-cell type prediction of transcription factor binding sites

Quang

2018

Genome Res.

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The ENCyclopedia of DNA Elements (ENCODE) consortium has generated transcription factor (TF) binding ChIP-seq data covering hundreds of TF proteins and cell types; however, due to limits on time and resources, only a small fraction of all possible TF-cell type pairs have been profiled. One solution is to build machine learning models trained on currently available epigenomic data sets that can be applied to the remaining missing pairs. A major challenge is that TF binding sites are cell-type–specific, which can be attributed to cellular contexts such as chromatin accessibility. Meanwhile, indirect TF-DNA binding and interactions between TFs complicate this regulatory process. Technical issues such as sequencing biases and batch effects render the prediction task even more challenging. Many pioneering efforts have been made to predict TF binding profiles based on DNA sequence and DNase-seq footprints, but to what extent a model can be generalized to completely untested cell conditions remains unknown. In this study, we describe our first place solution to the 2017 ENCODE-DREAM in vivo TF binding site prediction challenge. By carefully addressing multisource biases and information imbalance across cell types, we created a pipeline that significantly outperforms the current state-of-the-art methods. The proposed method is sufficiently complex enough to model nonlinear interactions between TF binding motifs and chromatin accessibility information up to 1500 bp from the genomic region of interest.

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Section: Distant Chromatin Architecture and Tf-tf Interactions Determmentioning

confidence: 99%

Anchor: trans-cell type prediction of transcription factor binding sites

Quang

2018

Genome Res.

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“…The E2F transcription factor family contains eight members, E2F1-8 (3). The present study identified the enriched signaling pathways of the eight E2F family genes, and the results revealed that the cell cycle signaling pathway was the most highly enriched ( Fig.…”

Section: E2f Family Genes Are Upregulated In Several Types Of Tumormentioning

confidence: 59%

“…E2F transcription factors include eight genes, E2F1-8 (1), which play critical roles in the regulation of cell proliferation and cell cycle progression through the mediated transcriptional activation of specific downstream target genes (2)(3)(4). E2F family genes also regulate autophagy (5), mitochondrial functions (6) and the DNA damage response (7).…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of the E2F transcription factors across cancer types

Wang

et al. 2020

Oncol Rep

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E2F transcription factors are associated with the development of cancer. However, the E2F family genes have not yet been studied in a comprehensive manner. Using The Cancer Genome Atlas, the present study analyzed the functions of the E2F family genes across different types of tumor. It was revealed that compared with normal tissues, the E2F family genes are highly expressed in several types of tumor tissue. Furthermore, E2F transcription factors were significantly enriched in tumor samples across different types of tumor. The high expression levels of E2F family genes were associated with an unfavorable prognosis in liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). Furthermore, patients with pathological T1 stage and iCluster2 molecular subtype of LIHC expressed particularly low levels of E2F family genes. The present study demonstrated that hypo-DNA methylation, DNA amplification and TP53 mutation contributed to the high expression levels of E2F family genes in cancer cells. Finally, the present study revealed that, compared with other types of tumor, the E2F family genes were specifically downregulated in patients with LIHC. The expression levels and prognostic effects of the E2F family genes were validated using the Gene Expression Omnibus database. The results of the present study revealed the biological functions of E2F family genes in the development of cancer and provided potential biomarkers for further therapeutic studies, particularly for patients with LIHC and LUAD.

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“…Both DBDs are necessary for the DNA binding ability of atypical E2Fs. Crystal structure analysis revealed that DBD1 and DBD2 bind to a typical E2F binding site in a manner similar to the E2F4/DP2 heterodimeric complex [62]. This suggests the possibility that atypical E2Fs are able to function as a monomer (Figure 4A).…”

Section: The Role Of Atypical E2fs In Endoreplication 41 Atypical E2mentioning

confidence: 93%

Distinct E2F-Mediated Transcriptional Mechanisms in Cell Proliferation, Endoreplication and Apoptosis

Komori¹,

Iwanaga²,

Bradford³

et al. 2019

Gene Regulation

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E2F and DP family proteins are evolutionally conserved transcription factors among higher eukaryotes. E2F and DP proteins typically form a heterodimeric complex, which controls cell proliferation by regulating expression of growthrelated genes. In addition, E2F family proteins have roles in various cellular events that require the expression of context-specific genes. E2F proteins use distinct mechanisms to regulate context-specific genes in different circumstances. The primary goal of this chapter is to compare three distinct mechanisms of mammalian E2F-mediated transcriptional regulation that control cell proliferation, endoreplication and apoptosis. Briefly, E2F7 and E2F8 control endoreplication by suppressing the expression of their target genes. They do not require DP or pRb. In control of apoptosis, E2F1 regulates the expression of the tumor suppressor gene Arf by binding to a non-canonical E2F binding site, within the Arf promoter, in a DP-independent manner. Furthermore, we examine the functions of E2F and DP in Drosophila melanogaster (fruit fly) to identify those mechanisms of E2F-mediated transcriptional regulation that have been evolutionarily conserved. The detailed mechanisms of how E2F protein regulates the expression of context-specific target genes will be instrumental in understanding how a single family of transcription factor regulates diverse pleiotropic cellular processes in an organism.

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Structural insights into the DNA-binding specificity of E2F family transcription factors

Cited by 58 publications

References 42 publications

Anchor: trans-cell type prediction of transcription factor binding sites

Anchor: trans-cell type prediction of transcription factor binding sites

Integrated analysis of the E2F transcription factors across cancer types

Distinct E2F-Mediated Transcriptional Mechanisms in Cell Proliferation, Endoreplication and Apoptosis

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