A map of direct TF–DNA interactions in the human genome

Gheorghe, Marius; Sandve, Geir Kjetil; Khan, Aziz; Chèneby, Jeanne; Ballester, Benoît; Mathelier, Anthony

doi:10.1093/nar/gkz582

Cited by 36 publications

(90 citation statements)

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“…Update and refinement of TF motif database warrant more accurate and comprehensive prediction of TF connectivity and network of TFs. Additional efforts can include incorporation of either publically available TF ChIP-seq data or TF ChIP-seq signals from cells of similar identity [ 87 ]. In supplement to the enhancer/NFR-centric CRC prediction, integrative analysis of genomic profiling, DNA methylome, chromatin compartmentalization, and enhancer-promoter interactions will extend and clarify regulatory loops.…”

Section: Resultsmentioning

confidence: 99%

Core transcriptional regulatory circuitries in cancer

Chen

Lin

et al. 2020

Oncogene

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Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type-specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics.

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Section: Resultsmentioning

confidence: 99%

Core transcriptional regulatory circuitries in cancer

Chen

Lin

et al. 2020

Oncogene

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“…TFs with an inconsistent signal for their different motifs were removed these are EGR1, MAFG, RARA, TLX1, TGIF1, VDR, TFDP1. We repeated the same procedure considering H3K27ac peaks that overlapped a TF-specific ChIP-Seq peak in the ChIP-Seq database from ReMap 2018 42 .…”

Section: Methodsmentioning

confidence: 99%

Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension

Reyes-Palomares

Grubert

et al. 2020

Nat Commun

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Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymaltransition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH.

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“…TFBSs enrichment analysis was also performed using JASPAR (JASPAR CORE vertebrates collection 2020), the largest open-access database of position-specific scoring matrices derived from experimentally validated TFBS [ 79 ], by selecting the predicted binding sites with a p -value ≥ 0.001, and UniBind, a comprehensive map of direct TF–DNA in the human genome based on public ChIP-seq datasets [ 80 ].…”

Section: Methodsmentioning

confidence: 99%

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

Zinghirino

Pappalardo

Messina

et al. 2020

IJMS

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VDACs (voltage-dependent anion-selective channels) are pore-forming proteins of the outer mitochondrial membrane, whose permeability is primarily due to VDACs’ presence. In higher eukaryotes, three isoforms are raised during the evolution: they have the same exon–intron organization, and the proteins show the same channel-forming activity. We provide a comprehensive analysis of the three human VDAC genes (VDAC1–3), their expression profiles, promoter activity, and potential transcriptional regulators. VDAC isoforms are broadly but also specifically expressed in various human tissues at different levels, with a predominance of VDAC1 and VDAC2 over VDAC3. However, an RNA-seq cap analysis gene expression (CAGE) approach revealed a higher level of transcription activation of VDAC3 gene. We experimentally confirmed this information by reporter assay of VDACs promoter activity. Transcription factor binding sites (TFBSs) distribution in the promoters were investigated. The main regulators common to the three VDAC genes were identified as E2F-myc activator/cell cycle (E2FF), Nuclear respiratory factor 1 (NRF1), Krueppel-like transcription factors (KLFS), E-box binding factors (EBOX) transcription factor family members. All of them are involved in cell cycle and growth, proliferation, differentiation, apoptosis, and metabolism. More transcription factors specific for each VDAC gene isoform were identified, supporting the results in the literature, indicating a general role of VDAC1, as an actor of apoptosis for VDAC2, and the involvement in sex determination and development of VDAC3. For the first time, we propose a comparative analysis of human VDAC promoters to investigate their specific biological functions. Bioinformatics and experimental results confirm the essential role of the VDAC protein family in mitochondrial functionality. Moreover, insights about a specialized function and different regulation mechanisms arise for the three isoform gene.

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A map of direct TF–DNA interactions in the human genome

Cited by 36 publications

References 0 publications

Core transcriptional regulatory circuitries in cancer

Core transcriptional regulatory circuitries in cancer

Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

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