Discuss The Estimation Of The Number Of Transcriptional Enhancers In The Human Genome, And How To Study Their Regulatory Activity

2067 words - 8 pages

Discuss the estimation of the number of transcriptional enhancers in the human genome, and how to study their regulatory activityWord Count : 1530IntroductionAn enhancer is a DNA region that can be bound with transcription factor protein or activators to up regulate transcription of a gene or genes (Pennacchio et al., 2013). Transcription of a gene refers to the start of gene expression when a particular DNA segment is transcribed into RNA using RNA polymerase. Enhancers are cis-acting and the human genome contains many of those regions. Enhancers belong to a class of transcriptional regulatory elements that includes promoters, silencers, insulators, and locus control regions. Enhancer's primary role is regulating the process of gene expression. Enhancers are hard to locate in the human genome as they are widely distributed (Pennacchio et al., 2013). They also contain poorly understood sequence features. Wide distribution and inability to understand enhancer region fully, leads to the difficulty in locating and computing the number of transcriptional enhancers (Pennacchio et al., 2013).Location of Transcriptional EnhancersEnhancers are located either upstream or downstream of the gene it regulates. It is not necessary for the enhancer to be near the transcription initiation site. Studies have found that some enhancers are located several thousand bases upstream or downstream from transcription initiation site (Pennacchio et al., 2013). Enhancers are bound by activator proteins/transcription factors in a cis-acting manner, and hence do not act in the promoter region (Shlyueva, Stampfel and Stark, 2014). Each octamer has about 147 base pair. Active enhancer and promoters can be identified by checking for depletion of nucleosome, some nucleosomes that flank active enhancers show specific histone modifications as shown in figure 1.a) Shows Intricate regulatory functions of the different enhancer (A and B), (4* 1 Histone core) (588 base pair) downstream are two transcription factors, one activating and repressive of gene x expression (enhancer A) serving a regulatory function , while further downstream three activating transcription factor are up regulating gene x expression. This also shows enhancer can be far away and still affect a particular gene.b, c) Shows DNA looping and inactivation of enhancers, (7* 1 Histone core) (1029 base pair) downstream, activating transcription factors are brought by DNA looping, which was hypothesised to be enzyme cohesin and other protein complexes, to the target promoters. The other enhancer was silenced by Polycomb protein-associated repressive H3K27me3 mark (b) or by repressive Transcription Factor binding (c).Only H3K4me1H3K4me1 and H3K27me3H3K4me1 and H3K27acH3K27ac and H3K4me3Specific Histone ModificationsFigure 1 (Shlyueva, Stampfel and Stark, 2014): The complex enhancer and its cis-acting behaviours.Enhancers play a key role in growth and development. Differentiation and growth of cells is a process that...

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