Computational approaches to understand transcription regulation in development
Maarten van der Sande, Siebren Frölich, Simon J van Heeringen1
1Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, 6525GA Nijmegen, The Netherlands.
Biochemical Society Transactions
|January 25, 2023
Summary
Computational methods for gene regulatory networks (GRNs) are improving with multi-omics, single-cell sequencing, and neural networks. These advances enhance accuracy for understanding gene regulation in development.
Area of Science:
- Genomics and Systems Biology
- Developmental Biology
- Bioinformatics
Background:
- Gene regulatory networks (GRNs) are crucial for understanding transcriptional dynamics during development.
- Current computational GRN inference methods, often based on gene expression data, suffer from inaccuracies and rely on correlative, not causative, interactions.
Approach:
- This review highlights advancements in GRN inference, focusing on three key areas: integrating multi-omics data, utilizing single-cell sequencing for cell-type-specific analysis, and employing neural networks as flexible modeling tools.
- These approaches move beyond traditional reliance on genome-wide gene expression alone.
Key Points:
- Multi-omics data integration provides a more comprehensive view of regulatory interactions.
- Single-cell sequencing enables the inference of context-specific GRNs by capturing cell type heterogeneity.
- Neural networks offer powerful and flexible modeling capabilities for complex regulatory relationships.
Conclusions:
- The synergy of multi-omics, single-cell technologies, and advanced computational models like neural networks promises to significantly improve the accuracy and reliability of inferred GRNs.
- Accurate GRN modeling is essential for elucidating the role of transcription factors in developmental processes and for generating testable hypotheses.
Keywords:
developmental biologyfunctional genomicsgene expression and regulationgene regulatory networksMore Related Videos
Related Concept Videos
Transcription
147.5K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
147.5K
Combinatorial Gene Control
8.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K
RNA Polymerase II Accessory Proteins
9.3K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.3K
Regulation of Expression at Multiple Steps
969
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
969
Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
Regulation of Expression Occurs at Multiple Steps
23.0K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
23.0K


