scholarly journals Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

2017 ◽  
Vol 421 (2) ◽  
pp. 93-107 ◽  
Author(s):  
Trevor L. Davis ◽  
Ilaria Rebay
Keyword(s):  
Gene Networks ◽  
Master Regulators ◽  
Retinal Determination ◽  
Pluripotency Gene

scholarly journals Identifying progressive gene network perturbation from single-cell RNA-seq data

2018 ◽  
Author(s):  
Sumit Mukherjee ◽  
Alberto Carignano ◽  
Georg Seelig ◽  
Su-In Lee
Keyword(s):  
Single Cell ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Simulated Data ◽  
Alternative Methods ◽  
Rna Seq ◽  
Differential Network Analysis ◽  
Master Regulators ◽  
Differential Network ◽  
Gene Regulatory

AbstractIdentifying the gene regulatory networks that control development or disease is one of the most important problems in biology. Here, we introduce a computational approach, called PIPER (ProgressIve network PERturbation), to identify the perturbed genes that drive differences in the gene regulatory network across different points in a biological progression. PIPER employs algorithms tailor-made for single cell RNA sequencing (scRNA-seq) data to jointly identify gene networks for multiple progressive conditions. It then performs differential network analysis along the identified gene networks to identify master regulators. We demonstrate that PIPER outperforms state-of-the-art alternative methods on simulated data and is able to predict known key regulators of differentiation on real scRNA-Seq datasets.

scholarly journals A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

2018 ◽  
Author(s):  
Stephen Wilson ◽  
Fabian V. Filipp
Keyword(s):  
Histone Modification ◽  
Transcriptional Activation ◽  
Gene Networks ◽  
Therapeutic Potential ◽  
Gene Promoter ◽  
Transcriptional Networks ◽  
Transcriptional Responses ◽  
Chromatin States ◽  
Master Regulators ◽  
Transcriptional Complex

AbstractCoordinated experiments focused on transcriptional responses and chromatin states are well-equipped to capture different epigenomic and transcriptomic levels governing the circuitry of a regulatory network. We propose a workflow for the genome-wide identification of epigenomic and transcriptional cooperation to elucidate transcriptional networks in cancer. Gene promoter annotation in combination with network analysis and sequence-resolution of enriched transcriptional motifs in epigenomic data reveals transcription factor families that act synergistically with epigenomic master regulators. A close teamwork of the transcriptional and epigenomic machinery was discovered. The network is tightly connected and includes the histone lysine demethylase KDM3A, basic helix-loop-helix factors MYC, HIF1A, and SREBF1, as well as differentiation factors AP1, MYOD1, SP1, MEIS1, ZEB1 and ELK1. In such a cooperation network, one component opens the chromatin, another one recognizes gene-specific DNA motifs, others scaffold between histones, cofactors, and the transcriptional complex. In cancer, due to the ability to team up with transcription factors, epigenetic factors concert mitogenic and metabolic gene networks, claiming the role of a cancer master regulators or epioncogenes.Specific histone modification patterns are commonly associated with open or closed chromatin states, and are linked to distinct biological outcomes by transcriptional activation or repression. Disruption of patterns of histone modifications is associated with loss of proliferative control and cancer. There is tremendous therapeutic potential in understanding and targeting histone modification pathways. Thus, investigating cooperation of chromatin remodelers and the transcriptional machinery is not only important for elucidating fundamental mechanisms of chromatin regulation, but also necessary for the design of targeted therapeutics.

Why is a new journal dedicated to vascular biology required?

2018 ◽  
Author(s):  
Paolo Madeddu
Keyword(s):  
Myocardial Ischemia ◽  
Tumor Growth ◽  
Vascular Tone ◽  
50Th Anniversary ◽  
Vascular Biology ◽  
Active Process ◽  
Master Regulators ◽  
Relaxing Factor ◽  
Tissue Healing ◽  
Endothelium Derived Relaxing Factor

The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.

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