STAT5 in regulation of chronic leukemia K562 cell proliferation: Inhibitory effect of WHI-P131

Mityushova, E. V.; Aksenov, N. D.; Marakhova, I I

doi:10.1134/s1990519x10010062

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…In contrast, transcription factors ZBTB33, ETS1, E2F4, SIX5 in GM12878 and TR4, SP2 and NRF1 in HepG2, which are enriched in single but depleted in redundant enhancers, are associated with repressor functions in gene expression [45–51]. In K562, the transcription factor E2F6, which might function as a repressor, is enriched in K562 single enhancers, while transcription factors STAT5, TAL1 and GATA2, which are all associated with growing culture and differentiation of leukemia cell, are significantly enriched in redundant enhancers [52–55] (Additional file 1: Figure S2A). These results indicate that single enhancers are enriched for a particular set of TFBSs, which are different from those in redundant enhancers and may not necessarily function as key factors of tissue-specificity, while redundant enhancers are specifically associated with tissue-specific biological processes.…”

Section: Resultsmentioning

confidence: 99%

Dichotomy in redundant enhancers points to presence of initiators of gene regulation

Song

Ovcharenko

2018

BMC Genomics

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BackgroundThe regulatory landscape of a gene locus often consists of several functionally redundant enhancers establishing phenotypic robustness and evolutionary stability of its regulatory program. However, it is unclear what mechanisms are employed by redundant enhancers to cooperatively orchestrate gene expression.ResultsBy comparing redundant enhancers to single enhancers (enhancers present in a single copy in a gene locus), we observed that the DNA sequence encryption differs between these two classes of enhancers, suggesting a difference in their regulatory mechanisms. Initiator enhancers, which are a subset of redundant enhancers and show similar sequence encryption to single enhancers, differ from the rest of redundant enhancers in their sequence encryption, evolutionary conservation and proximity to target genes. Genes hosting initiator enhancers in their loci feature elevated levels of expression. Initiator enhancers show a high level of 3D chromatin contacts with both transcription start sites and regular enhancers, suggesting their roles as primary activators and intermediate catalysts of gene expression, through which the regulatory signals of redundant enhancers are propagated to the target genes. In addition, GWAS and eQTLs variants are significantly enriched in initiator enhancers compared to redundant enhancers, suggesting a key functional role these sequences play in gene regulation.ConclusionsThe specific characteristics and widespread abundance of initiator enhancers advocate for a possible universal hierarchical mechanism of tissue-specific gene regulation involving multiple redundant enhancers acting through initiator enhancers.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5335-0) contains supplementary material, which is available to authorized users.

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