Curated by RSF Research Staff
Researchers identify crucial mechanism delimiting functional domains of a genome – new understanding of how DNA is managed to produce specific cell functions.
Genes make proteins, and specific sets of proteins define tissue-type: for instance, you wouldn’t expect to find proteins for hemoglobin in neuronal cells and conversely you wouldn’t expect to find proteins that make voltage-gated ion channels in red blood cells. These functional elements of the cell, along with a cadre of other cell-specific proteins, are responsible for making a neuron a neuron and a red blood cell (erythrocyte) a red blood cell. Yet, both cell-types have the genes for each of these cell-specific proteins, in fact every nucleated cell in the body contains a full set of all tissue-specific genes as part of the full genome. Tissue-specificity must then arise from how genes are differentially expressed, meaning that in some cell lineages certain sets of genes are silenced, while in others they are expressed – leading one line of progenitor (stem) cells to differentiate into neurons and another to differentiate into erythrocytes, or any of the other approximately 200 different cell types of the human body.
This is one example of a critical emergent understanding in the fields of molecular genetics and morphogenesis, known as epigenetics. Epigenetics is a reference to a whole host of mechanisms that effect cellular function, tissue-specificity, and morphogenesis above and beyond the genetic code specified in the linear sequence of DNA nucleotides. Essentially, the defining characteristic of complex genomes is not so-much what is specified in the genetic code, but how it is expressed.
A particularly critical epigenetic mechanism regards: the linear organization of genetic domains along chromosomal strands; the three-dimensional organization of chromosomal regions and the genome within the nucleus; and the four-dimensional spatiotemporal expression of specific gene regions. A recent study published in Nature Cell Biology has shed new light on the linear organization delimiting specific genetic domains. The research team found that molecular markers, known as CTCF--cohesion-binding sites partition chromosomes into 1—5 megabase (1 to 5 million base-pair regions) topologically associated domains. The binding of a molecule called CTCF to the recognition sites is critical for identifying and maintaining these specific domains during reading of the genome. Disruption of the interaction can lead to expression of genes outside of the domains specified by the CTCF--cohesion-binding sites which can disrupt proper expression of tissue-specific proteins, leading to aberrant cellular function.