What parts of the genome are reversibly methylated? How does this affect gene expression?

Epigenetics involves changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. One of the most widely studied epigenetic mechanisms is DNA methylation. In this process, methyl groups are added to the DNA molecule, typically at cytosine bases near guanine bases, creating what's known as CpG sites. This does not change the sequence of the DNA but can impact how easily DNA is accessed and thus how genes are expressed.

Over time, environmental factors and developmental signals can influence the methylation patterns in an organism's genome. This is crucial for normal development as well as for the adaptation of organisms to a changing environment over their lifetime. Interestingly, while some methylation patterns are stable and may even be passed down across generations, others are reversible, allowing for a flexible response to external and internal signals.

The ability of a cell to regulate the expression of its genes is fundamental to its proper function. Gene expression regulation is the process by which cells control the amount and timing of the appearance of the functional product of a gene. This regulation can occur at any point during gene expression but is most commonly modulated during transcription, where the role of reversible methylation comes into play.

When specific gene regions are methylated, the expression of the gene can be reduced or silenced, as the methyl groups interfere with the ability of transcription factors to bind to the DNA. In contrast, when these methyl groups are removed, transcription factors are able to bind, leading to gene activation. The nuanced balance of methylation and demethylation over the lifespan of an organism is a key part of the development, cellular differentiation, and adaptation to environmental changes.

CpG islands are regions in the DNA with a high frequency of CG dinucleotides where the cytosine is located next to a guanine in the linear sequence of bases. These islands are often located near or within the promoter regions of genes and play a significant role in the initiation of gene expression. In normal cells, CpG islands in promoter regions are usually unmethylated, allowing for the binding of transcription factors and the subsequent transcription of the associated gene.

When these CpG islands become methylated, however, the expression of the gene can be downregulated or entirely silenced. This pattern of methylation is a crucial component of gene regulation, particularly in controlling genes that should not be expressed in certain tissues or at certain developmental stages. Aberrant methylation of CpG islands is also associated with various diseases, including cancer.

DNA demethylases are enzymes responsible for the removal of methyl groups from methylated DNA, a process known as demethylation. The ability to reverse DNA methylation is pivotal in gene expression regulation. One known family of proteins that can demethylate DNA are the TET (Ten-Eleven Translocation) enzymes, which convert the methylated cytosine to 5-hydroxymethylcytosine and further promote demethylation.

This demethylation process is essential for the activation of genes that have been silenced by methylation and is particularly important during embryonic development and in the fine-tuning of genes related to cell differentiation. The dynamic nature of methylation and demethylation underscores the complexity of the epigenetic control of gene expression and allows cells to respond to and integrate various internal and external signals.