Systems-level identification of transcription factors critical for mouse embryonic development

Abstract

Dynamic changes in the transcriptional regulatory circuit can influence the specification of distinct cell types. Numerous transcription factors (TFs) have been shown to function through dynamic rewiring during embryonic development but a comprehensive survey on the global regulatory network is still lacking. Here, we performed an integrated analysis of epigenomic and transcriptomic data to reveal key regulators from 2 cells to postnatal day 0 in mouse embryogenesis. We predicted 3D chromatin interactions including enhancer-promoter interactions in 12 tissues across 8 developmental stages, which facilitates linking TFs to their target genes for constructing genetic networks. To identify driver TFs particularly those not necessarily differentially expressed ones, we developed a new algorithm, dubbed as Taiji, to assess the global importance of TFs in development. Through comparative analysis across tissues and developmental stages, we systematically uncovered TFs that are critical for lineage-specific and stage-dependent tissue specification. Most interestingly, we have identified TF combinations that function in spatiotemporal order to form transcriptional waves regulating developmental progress and differentiation. Not only does our analysis provide the first comprehensive map of transcriptional regulatory circuits during mouse embryonic development, the identified novel regulators and the predicted 3D chromatin interactions also provide a valuable resource to guide further mechanistic studies.

Insight into DNA Methylation

“…It has become a new challenge for the new generation of medical science to prepare the most effective drug for the proper treatment of different types of cancers [1][2][3][4][5][6][7] . To make the treatment, more effective medical scientists have tried to increase the use of nanoparticles so that drug delivery into the exact location becomes possible.…”

QTsome for therapeutic delivery of miRNA for cancer

“…To minimize these issues, the introduction of nanoparticles is the only way out. Introduction of nanoparticles with the chemotherapeutic drug is not only helping to detect the disease at an early stage but also making sure the speedy recovery of the patient [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . Hence, nanoparticles are used as the prime ingredient in the chemotherapeutic drug incorporated into the human body.…”

Nanoparticle therapeutics: a new treatment of cancer

“…To control the multi-drug resistance (MDR), the process to introduce multiple chemotherapeutic drugs is used nowadays. Apart from this, nanoparticles used for antipsychotic disease treatment is comparatively low while it is mainly used for cancer treatment [45][46][47][48][49][50][51] . This is only for the lack of knowledge about psychosis that restricts the drugs from being designed.…”