Regulation of Gene Expression
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As we have noted earlier, cells in multicellular organisms can express different sets of genes defining cells' specific functions and structural features. Expression can be regulated at any step leading from a gene to a protein and even at the proceeding steps of protein inactivation and degradation. We have previously outlined the RNA processing control resulting in diverse RNA splicing products, however, for most genes, the control at the transcription level is of primary importance.
The regulation of gene expression through altering chromatin structure determines the accessibility of genes and their promoters to the transcription machinery. Genes situated in dense chromatin regions, known as heterochromatin, are typically inaccessible for transcription. In contrast, genes located in decondensed chromatin regions (euchromatin), can be transcribed, with the level of transcription influenced by factors such as nucleosome positioning, histone modifications, and modifications of nucleotides in the DNA.
One common histone modification that influences chromatin structure is histone acetylation, where acetyl groups are added to lysine side chains, removing their positive charge. This modification reduces the affinity of histones for DNA, resulting in chromatin opening and increased accessibility of DNA for transcription-related proteins, thus enhancing gene expression.
A prevalent nucleotide modification in eukaryotes is cytosine methylation. Methylated genes are typically inactive, and their demethylation leads to gene activation and increased expression.
DNA methylation and histone modifications, despite being reversible, can be transmitted to daughter cells during cell division. This type of inheritance, which involves the transmission of information that is not encoded in the DNA sequence itself but rather in the modifications of DNA and histones, is called epigenetic inheritance.
The initiation of transcription of all protein-coding genes in eukaryotes relies on a set of proteins known as general transcription factors, which bind to the promoter region. However, for genes with tissue-specific expression patterns, additional transcription factors are required. These specialised transcription factors bind to specific DNA sequences and either facilitate or block the binding of RNA polymerase, thus regulating transcription initiation.
Transcription factors that enhance transcription are called activators, and they bind to enhancer sequences in the DNA. Conversely, transcription factors that inhibit transcription are termed repressors, and they bind to silencer sequences.
Each transcription factor typically regulates multiple genes. However, activation of a particular gene's expression depends on the specific combination of transcription factors present (in the case of activators) or absent (in the case of repressors). This intricate network of transcription factors ensures precise control over gene expression in response to cellular signals and developmental cues.
Alterations in gene expression within a cell can occur through various mechanisms in response to numerous internal and external stimuli. One common example is the cell's response to a chemical stimulus, such as a hormone.
In this scenario, a hormone typically binds to a receptor located on the cell's surface. This binding event induces a conformational change in the receptor, initiating a cascade of molecular events within the cell known as a signal transduction pathway. Eventually, this pathway leads to the activation of specific transcription factors.
Once activated, these transcription factors modulate gene expression by binding to the regulatory regions of their target genes. This binding alters the expression levels of these genes, thereby implementing the response to the initial stimulus.
