Regulome

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Regulome refers to the whole set of regulatory components in a cell. [1] Those components can be regulatory elements, genes, mRNAs, proteins, and metabolites. The description includes the interplay of regulatory effects between these components, and their dependence on variables such as subcellular localization, tissue, developmental stage, and pathological state.

Contents

Components

One of the major players in cellular regulation are transcription factors, proteins that regulate the expression of genes. [2] Other proteins that bind to transcription factors to form transcriptional complexes might modify the activity of transcription factors, for example blocking their capacity to bind to a promoter.

Signaling pathways are groups of proteins that produce an effect in a chain that transmit a signal from one part of the cell to another part, for example, linking the presence of substance at the exterior of the cell to the activation of the expression of a gene.

Measuring

High-throughput technologies for the analysis of biological samples (for example, DNA microarrays, proteomics analysis) allow the measurement of thousands of biological components such as mRNAs, proteins, or metabolites. [3] Chromatin immunoprecipitation of transcription factors can be used to map transcription factor binding sites in the genome. [4]

Such techniques allow researchers to study the effects of particular substances and/or situations on a cellular sample at a genomic level (for example, by addition of a drug, or by placing cells in a situation of stress). The information obtained allows parts of the regulome to be inferred.

Modeling

One of the objectives of systems biology is the modeling of biological processes using mathematics and computer simulation. [5] The production of data from techniques of genomic analysis is not always amenable to interpretation mainly due to the complexity of the data and the large number of data points. Modeling can handle the data and allow to test a hypothesis (for example, gene A is regulated by protein B) that can be verified experimentally.

Applications

The complete knowledge of the regulome will allow researchers to model cell behaviour entirely. This will facilitate the design of drugs for therapy, [6] the control of stem cell differentiation, and the prognosis of disease.

See also

Related Research Articles

Bioinformatics Computational analysis of large, complex sets of biological data

Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combines biology, chemistry, physics, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data. Bioinformatics has been used for in silico analyses of biological queries using mathematical and statistical techniques.

Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

Transcription factor Protein that controls the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

Gene expression Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication.

Alternative splicing Process by which a single gene can code for multiple proteins

Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions. Notably, alternative splicing allows the human genome to direct the synthesis of many more proteins than would be expected from its 20,000 protein-coding genes.

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

Systems biology Computational and mathematical modeling of complex biological systems

Systems biology is the computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a holistic approach to biological research.

Regulation of gene expression

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

DNA-binding protein Proteins that bind with DNA, such as transcription factors, polymerases, nucleases and histones

DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However, there are some known minor groove DNA-binding ligands such as netropsin, distamycin, Hoechst 33258, pentamidine, DAPI and others.

Functional genomics Field of molecular biology

Functional genomics is a field of molecular biology that attempts to describe gene functions and interactions. Functional genomics make use of the vast data generated by genomic and transcriptomic projects. Functional genomics focuses on the dynamic aspects such as gene transcription, translation, regulation of gene expression and protein–protein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structures. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional "gene-by-gene" approach.

The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The term transcriptome is a portmanteau of the words transcript and genome; it is associated with the process of transcript production during the biological process of transcription.

Regulator gene

A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. Regulatory sequences, which encode regulatory genes, are often at the five prime end (5') to the start site of transcription of the gene they regulate. In addition, these sequences can also be found at the three prime end (3') to the transcription start site. In both cases, whether the regulatory sequence occurs before (5') or after (3') the gene it regulates, the sequence is often many kilobases away from the transcription start site. A regulator gene may encode a protein, or it may work at the level of RNA, as in the case of genes encoding microRNAs. An example of a regulator gene is a gene that codes for a repressor protein that inhibits the activity of an operator.

ChIP-on-chip Molecular biology method

ChIP-on-chip is a technology that combines chromatin immunoprecipitation ('ChIP') with DNA microarray ("chip"). Like regular ChIP, ChIP-on-chip is used to investigate interactions between proteins and DNA in vivo. Specifically, it allows the identification of the cistrome, the sum of binding sites, for DNA-binding proteins on a genome-wide basis. Whole-genome analysis can be performed to determine the locations of binding sites for almost any protein of interest. As the name of the technique suggests, such proteins are generally those operating in the context of chromatin. The most prominent representatives of this class are transcription factors, replication-related proteins, like origin recognition complex protein (ORC), histones, their variants, and histone modifications.

ChIP-sequencing, also known as ChIP-seq, is a method used to analyze protein interactions with DNA. ChIP-seq combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to identify the binding sites of DNA-associated proteins. It can be used to map global binding sites precisely for any protein of interest. Previously, ChIP-on-chip was the most common technique utilized to study these protein–DNA relations.

Tiling array

Tiling arrays are a subtype of microarray chips. Like traditional microarrays, they function by hybridizing labeled DNA or RNA target molecules to probes fixed onto a solid surface.

Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.

Chromatin Interaction Analysis by Paired-End Tag Sequencing is a technique that incorporates chromatin immunoprecipitation (ChIP)-based enrichment, chromatin proximity ligation, Paired-End Tags, and High-throughput sequencing to determine de novo long-range chromatin interactions genome-wide.

Chromatin immunoprecipitation

Chromatin immunoprecipitation (ChIP) is a type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. It aims to determine whether specific proteins are associated with specific genomic regions, such as transcription factors on promoters or other DNA binding sites, and possibly defining cistromes. ChIP also aims to determine the specific location in the genome that various histone modifications are associated with, indicating the target of the histone modifiers.

The NAS Award in Molecular Biology is awarded by the U.S. National Academy of Sciences "for recent notable discovery in molecular biology by a young scientist who is a citizen of the United States." It has been awarded annually since its inception in 1962.

The Centre for Genomic Regulation is a biomedical and genomics research centre based on Barcelona. Most of its facilities and laboratories are located in the Barcelona Biomedical Research Park, in front of Somorrostro beach.

References

  1. Singh, Prithipal (2019). Biodiversity, Conservation and Systematics. Scientific Publishers. p. 209. ISBN   9388449738.
  2. Lee, Tong Ihn; Young, Richard A. (March 2013). "Transcriptional Regulation and Its Misregulation in Disease". Cell. 152 (6): 1237–1251. doi:10.1016/j.cell.2013.02.014. hdl: 1721.1/103908 .
  3. "Technologies used in functional genomic studies | Functional genomics" . Retrieved 30 September 2021.
  4. Collas, Philippe (May 2010). "The Current State of Chromatin Immunoprecipitation". Molecular Biotechnology. 45 (1): 87–100. doi:10.1007/s12033-009-9239-8.
  5. Tavassoly, Iman; Goldfarb, Joseph; Iyengar, Ravi (26 October 2018). "Systems biology primer: the basic methods and approaches". Essays in Biochemistry. 62 (4): 487–500. doi:10.1042/EBC20180003.
  6. "An integrated systems-level framework for deciphering multidrug resistant epilepsy" . Retrieved 30 September 2021.