LCRs controlled human globin genes such as beta, delta, gamma-A, gamma-G, and epsilon globin and the genes are differentially expressed throughout development.
The order of these genes in the beta-globin cluster are:
5' - epsilon – gamma-G – gamma-A – delta – beta - 3'.
This arrangement affects the temporal differentiation of expression during development and the early-embryonic stage of gene which is located closest to the LCR. And if the genes are rearranged then the gene products are expressed at improper stages of development.
LCR controls expression of linked genes at distal chromatin sites. It is copy number-dependent manner, tissue-specific.
Models regulate expression of Human globin genes with LCR :
1) Looping model :
When transcription factors bind to hypersensitive site then LCR form a loop and interact with the promoter of the gene
2) Tracking model :
When transcription factors bind to the LCR then it forms a complex and this complex moves along the DNA helix and bind to the promoter of the gene and increases gene expression.
3) Facilitated tracking model :
This combines the looping and tracking models. Here whhen transcription factors bind to the LCR , it form a loop that binds to the promoter of the gene.
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