ATF4-dependent Regulation of the JMJD3 Gene during Amino Acid Deprivation Can Be Rescued in Atf4-deficient Cells by Inhibition of Deacetylation

Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

“…The present results for ATF4, illustrating rapid association with the ATF3 gene, are consistent with our previously published ChIP analysis (28). Recently, we have discovered that while transcription from the ATF3 gene is severely reduced in Atf4-deficient MEF, the elevated transcription activity can be rescued by chemical inhibition of deacetylation to increase histone H4 acetylation at the ATF3 gene (29). Those observations, consistent with the present data, suggest that a primary function of ATF4 action on the ATF3 gene is to enhance acetylation by enhancing a HAT or inhibiting a histone deacetylase.…”

“…An additional area for future investigation is the comparison of these pathways and control mechanisms in hepatoma cells such as HepG2 and normal human hepatocytes. The activation of the ATF4-dependent AAR pathway is known to exist in primary human hepatocytes (29), but that for cJUN is suppressed relative to transformed cells (10).…”

Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B

“…Here, we focused on the functional significance of changes in CSL levels in skin and head and neck epithelial cells. of KDM6B by NF-KB and STATs observed in other cell types (36,38,70,72,73) may also apply to squamous cancer, which is often associated with and can be induced by inflammation (74). Targeting epigenetic regulators is emerging as promising cancer therapy.…”

Endoplasmic reticulum proteostasis in glioblastoma—From molecular mechanisms to therapeutic perspectives

“…UPR-mediated gene expression also involves chromatin remodeling by directly acting on histone modifications. For instance, the gene encoding Jumonji domain-containing 3 histone lysine demethylase [JMJD3; also known as lysine (K)-specific demethylase 6B (KDM6B)] is an ATF4 target gene (79). Moreover, chaetocin (a nonspecific inhibitor of histone lysine methyltransferases) increases ATF3 and CHOP expression, leading to DR5-dependent apoptosis of lung cancer cells (80), thereby linking ER stress to epigenetic regulation.…”

“…For instance, ATF6 activates transcription of ER stress response genes through the recruitment of several HAT complexes including SAGA and Ada2a-containing (ATAC) molecules (86,87). Transcription of ATF4 target genes CHOP, ATF3, and JMJD3 requires HAT activity (79). Under ER stress, the SAGA complex increases acetylation of the histone H3K14 and maintains trimethylation of histone H3K4 on ER stressinduced genes, thus allowing their transcription (88).…”