The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans

Abstract

SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity in C. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. HCF-1 localization at chromatin is largely dependent on functional SET-26, whereas SET-26 is only minorly affected by loss of HCF-1, suggesting that SET-26 could recruit HCF-1 to chromatin. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.

Can O-GIcNAc Transferase (OGT) Complex Be Used as a Target for the Treatment of Hematological Malignancies?

“…HCF-1, which was first isolated from the human herpes simplex virus, is a transcriptional cofactor that regulates the indicated target gene transcription, such as the cell cycle regulatory proteins E2 promoter binding factors (E2Fs) [ 66 ], the maintenance of the embryonic stem cell pluripotency factor Ronin [ 67 ], and the regulatory proteins for glucose metabolism proliferator-activated receptor-gamma coactivator-1 (PGC-1) [ 68 ] and forkhead box O (FOXO) [ 69 ], which in turn are involved in the regulation of embryonic stem cell pluripotency, cell cycle progression, cell proliferation, and metabolic stress. Studies have shown that high expression of HCF-1 is a marker for poor prognosis in the treatment of malignancies such as primary prostate tumors, lymphomas, AML, and sarcoid lymphomas [ 70 ].…”