Cis-regulatory elements, such as insulators, promoters, silencers and enhancers, are sequences of non-coding DNA, which act as a sequence-specific binding site for protein, such as transcriptional factors (TFs), resulting in the regulation of the gene transcription. Particularly, enhancers are known for their ability to significantly increase the level of transcription of a particular gene and therefore its expression (Banerji et al., 1981). Enhancer sequences can be located up to thousands of kilobases upstream or downstream from a relevant gene, moreover enhancers can also be found within a gene (Pennachio et al., 2013 and Heintzman et al., 2009).
In 2004 IHGSC released a fully sequenced human genome and estimated the number of protein-coding genes to be 20,000-25,000. Considering the fact that all somatic cell of an organism have the same DNA content, and therefore the same number of genes, the ultimate task for a cell should be to control the gene expression in cell-type-specific and tissue-specific manner. Enhancers serve as one of tools for achieving this goal. Heintzman et al. (2009) found that the number of enhancers identified only from two cell lines already far exceeded the number of protein-coding genes and predicted the approximate number of enhancers in the human genome to be 1 x 106. The accuracy of this estimation will be discussed later as well as the shortcomings of the methods used. Furthermore, additional approaches to validate enhancers identification will be considered.
Heintzman et al. (2009) used markers, such as CTCF insulator protein...
... middle of paper ...
...? Molecular cell, 49(5): 825-837.
Grifﬁths A. J. F., et al. (2011). Introduction to Genetic Analysis (10th edition). New York: W. H. Freeman.
Heintzman, N.D. et al. (2009). Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459: 108-112.
International Human Genome Sequencing Consortium. (2004). Finishing the euchromatic sequence of the human genome. Nature 431(7011): 931-945.
Pennachio, L.A. et al. (2013). Enhancers: five essential questions. Nature Reviews Genetics 14: 288-295.
Shlyueva, D. et al. (2014). Transcriptional enhancers: from properties to genome-wide predictions. Nature Reviews Genetics 15: 272-286.
Wang, Q., Carroll, J. S., & Brown, M. (2005). Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Molecular cell 19(5): 631-642.
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