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In "Function"

There are certain highly conserved, hypersensitive (HS) binding sites in globin genes that are necessary for proper function. In these hypersensitive sites, the DNA configuration is more open, allowing access to the DNA by binding proteins which can influence transcription. The conserved nature of these sites implies that they are functionally necessary. This does not extend to say that non-conserved regions are not functionally necessary, however. These non-conserved regions could have arisen as specific to the gene expression pattern of a particular species, which can be seen in the differing regulation patterns of globin gene expression in development in humans and mice.

The most widely studied aspect of the concept of the LCR is when taken in context with β-globin gene regulation. The concept of the LCR stemmed from human and mouse globin research, and how it plays are role in regulation of developmental gene expression. The LCR comprises part of the entire gene locus, and plays a key role in regulating expression of transcribed genes. The most prominent property of the LCR is it's ability to affect the transcriptional enhancement of a gene. Although it cannot be said that the LCR directly influences basal transcription (whether or not a gene is transcribed at all), it has been shown to have significant effects on transcriptional enhancement, as shown in studies of transgenic mice, where an absence of the LCR lead to β-globin gene expression levels of less than 1% of that of the comparable endogenous mouse β-globin gene, if it was expressed at all. Conversely, the inclusion of the LCR showed equal levels of human β-globin gene expression in transgenic animals, when compared to the endogenous levels of mouse β-globin, indicating that the LCR is involved in gene enhancer activity.

Another significant property of the LCR is that it confers position-independent, copy number dependent expression on linked genes, which is considered to be indicative of an open-chromatin configuration. In research directed towards β-thalassemia, LCR deletion mutants were shown to have β-globin gene inactivation, indicating that with a deletion, chromatin is not in open configuration, and therefore not accessible to transcription factors. A small deletion on the locus can leave the entire locus in closed chromatin configuration, even though the remainder of the locus that was unaffected by the deletion is still intact. The ability to confer copy-number dependent expression of a transgene is used as criterion to identify if a DNA fragment is functioning as an LCR rather than a transcriptional enhancer in the identification of LCR or similar elements. The LCR's function is cell specific, being seen widely in erythroid cells. This is evidenced by the fact that the LCR is most widely studied when in context with the β-globin gene, and β-thalassemia, therefore having the most evidence on its function and position in relation to human and mouse β-globin gene systems.

In "Diseases related to the LCR"

In studies conducted to determine the relationship between the LCR and β-globin gene expression, it was oberserved that a large deletion upstream of the β-globin gene results in the silencing of that gene. Although still intact, the genes are transcriptionally inactive due to the DNA of the entire locus being in a heterochromatic state, resulting in certain forms of β-thalassemia.