# Regulation of Gene Expression 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. ## Chromatin regulation 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.

Histone acetylation results in opening up chromosome
Image source:
Eslaminejad, Mohamadreza & Fani, Nesa & Shahhoseini, Maryam. (2013). Epigenetic Regulation of Osteogenic and Chondrogenic Differentiation of Mesenchymal Stem Cells in Culture. Cell Journal. 15. 1-10.

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**. ## Transcription factors 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 activators bind the enhancer to promote the expression of a gene
Image source:
CNX OpenStax - http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introduction, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=49929334

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.

A combination of transcription factors is often required to initiate gene expression
Image source:
Untitled image. "Combinatorial control". Accessed April 17, 2024.
https://www.khanacademy.org/science/biology/gene-expression-central-dogma/translation-polypeptides/a/the-stages-of-translation

## Activation of transcription factors 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.

Activation of a transcription factor through a signal transduction pathway
Image source:
Untitled image. "Transcription and DNA-Protein Binding". Accessed April 17, 2024.
https://biologicalmodeling.org/motifs/transcription
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0

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. ## Transcriptome [One of the ways to measure gene expression is the quantification of different RNA molecules present in a sample using sequencing-based approaches. The whole set of RNA molecules in a tissue sample or an organism is called the transcriptome.](#user-content-fn-1)[^1] [^1]: Not sure we need it really --- # Agent Instructions: Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter: ``` GET https://edu.abi.am/molecular-biology/information-flow-in-the-cell/regulation-of-gene-expression.md?ask= ``` The question should be specific, self-contained, and written in natural language. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.