Core promoter STRs: Novel mechanism for inter-individual variation in gene expression in humans

Heidari, Abolfazl; Nariman‐Saleh‐Fam, Ziba; Esmaeilzadeh-Gharehdaghi, Elika; Banan, Mehdi; Hosseinkhani, Saman; Mohammadparast, Saeid; Oladnabi, Morteza; Ebrahimpour, Mohammad Reza; Soosanabadi, Mohsen; Farokhashtiani, T.; Darvish, Hossein; Firouzabadi, Saghar Ghasemi; Farashi, Samaneh; Najmabadi, Hossein; Ohadi, Mina

doi:10.1016/j.gene.2011.10.028

Cited by 26 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have recently reported human core promoter STRs that are exceptionally long, and may be of selective advantage (Darvish et al 2011;Ohadi et al, 2012a). This notion is supported by the emerging evidence of functionality for a number of those STRs, to modulate gene expression (Valipour et al, 2013;Heidari et al, 2012), and their differential evolution in the primate order vs. other mammals (Ohadi et al, 2015;Rezazadeh et al, 2014;Mohammadparast et al 2014). …”

Section: Discussionmentioning

confidence: 76%

Exceptionally long 5′ UTR short tandem repeats specifically linked to primates

Namdar-Aligoodarzi

Mohammadparast

Zaker-Kandjani

et al. 2015

Gene

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 76%

Exceptionally long 5′ UTR short tandem repeats specifically linked to primates

Namdar-Aligoodarzi

Mohammadparast

Zaker-Kandjani

et al. 2015

Gene

Self Cite

View full text Add to dashboard Cite

“…Hence, our findings of profound changes in STR period, repeat unit number and base composition around the TSS of human genes is interesting given the findings in yeast and indicate that similar mechanisms of regulating gene expression may be at play in the human genome [52]. In this regard, a recent study has shown that a polymorphic GA-repeat in the human SOX5 gene promoter can affect gene expression, with the longer allele resulting in a 2.7-fold increase in activity [53]. The authors report this as first evidence of a functional STR in a human gene core promoter [53].…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, a recent study has shown that a polymorphic GA-repeat in the human SOX5 gene promoter can affect gene expression, with the longer allele resulting in a 2.7-fold increase in activity [53]. The authors report this as first evidence of a functional STR in a human gene core promoter [53]. …”

Section: Discussionmentioning

confidence: 99%

STaRRRT: a table of short tandem repeats in regulatory regions of the human genome

et al. 2013

View full text Add to dashboard Cite

BackgroundTandem repeats (TRs) are unstable regions commonly found within genomes that have consequences for evolution and disease. In humans, polymorphic TRs are known to cause neurodegenerative and neuromuscular disorders as well as being associated with complex diseases such as diabetes and cancer. If present in upstream regulatory regions, TRs can modify chromatin structure and affect transcription; resulting in altered gene expression and protein abundance. The most common TRs are short tandem repeats (STRs), or microsatellites. Promoter located STRs are considerably more polymorphic than coding region STRs. As such, they may be a common driver of phenotypic variation. To study STRs located in regulatory regions, we have performed genome-wide analysis to identify all STRs present in a region that is 2 kilobases upstream and 1 kilobase downstream of the transcription start sites of genes.ResultsThe Short Tandem Repeats in Regulatory Regions Table, STaRRRT, contains the results of the genome-wide analysis, outlining the characteristics of 5,264 STRs present in the upstream regulatory region of 4,441 human genes. Gene set enrichment analysis has revealed significant enrichment for STRs in cellular, transcriptional and neurological system gene promoters and genes important in ion and calcium homeostasis. The set of enriched terms has broad similarity to that seen in coding regions, suggesting that regulatory region STRs are subject to similar evolutionary pressures as STRs in coding regions and may, like coding region STRs, have an important role in controlling gene expression.ConclusionsSTaRRRT is a readily-searchable resource for investigating potentially polymorphic STRs that could influence the expression of any gene of interest. The processes and genes enriched for regulatory region STRs provide potential novel targets for diagnosing and treating disease, and support a role for these STRs in the evolution of the human genome.

show abstract

“…We have recently identified exceptional purine island human promoter compositions (albeit in the proximal core promoter region) with sequence bias between human and mouse (Darvish et al, 2011), and shown that haplotypes across those purine complexes can significantly alter gene expression (Heidari et al, 2012). The mechanistic events mediating altered gene expression as a result of different haplotypes across CAV1 upstream purine complex remain to be clarified in future studies.…”

Section: Discussionmentioning

confidence: 97%