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Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers.

ABSTRACT: Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (

SUBMITTER: Sanchez GJ 

PROVIDER: S-EPMC5829637 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers.

Sanchez Gilson J GJ   Richmond Phillip A PA   Bunker Eric N EN   Karman Samuel S SS   Azofeifa Joseph J   Garnett Aaron T AT   Xu Quanbin Q   Wheeler Graycen E GE   Toomey Cathryn M CM   Zhang Qinghong Q   Dowell Robin D RD   Liu Xuedong X  

Nucleic acids research 20180201 4

Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of  ...[more]

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