Drosophila melanogaster dHCF Interacts with both PcG and TrxG Epigenetic Regulators

Abstract

Repression and activation of gene transcription involves multiprotein complexes that modify chromatin structure. The integration of these complexes at regulatory sites can be assisted by co-factors that link them to DNA-bound transcriptional regulators. In humans, one such co-factor is the herpes simplex virus host-cell factor 1 (HCF-1), which is implicated in both activation and repression of transcription. We show here that disruption of the gene encoding the Drosophila melanogaster homolog of HCF-1, dHCF, leads to a pleiotropic phenotype involving lethality, sterility, small size, apoptosis, and morphological defects. In Drosophila, repressed and activated transcriptional states of cell fate-determining genes are maintained throughout development by Polycomb Group (PcG) and Trithorax Group (TrxG) genes, respectively. dHCF mutant flies display morphological phenotypes typical of TrxG mutants and dHCF interacts genetically with both PcG and TrxG genes. Thus, dHCF inactivation enhances the mutant phenotypes of the Pc PcG as well as brm and mor TrxG genes, suggesting that dHCF possesses Enhancer of TrxG and PcG (ETP) properties. Additionally, dHCF interacts with the previously established ETP gene skd. These pleiotropic phenotypes are consistent with broad roles for dHCF in both activation and repression of transcription during fly development.

Dual functionality of O -GlcNAc transferase is required for Drosophila development

“…The most prevalent defect observed was for ectopic vein arising from the posterior cross-vein in rescues with almost all the constructs. Interestingly, similar ectopic vein phentotype, arising from the posterior cross-vein, is observed in Drosophila HCF ( dHCF ) mutants [ 41 ]. With dHCF being an OGT substrate, it is possible that sub-optimal O -GlcNAcylation of dHCF leads to the ectopic vein phenotype.…”

Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation

“…HCF, which is necessary for proper cell cycle progression, interacts with both Pc and Trx groups in Drosophila (52). Moreover, SET1 activity is regulated by HCF1 in mammals and HCF1 activity is regulated by O-GlcNAcylation (14,27,53).…”

Role of Host Cell Factor-1 in cell cycle regulation.

“…Recent studies implicate HCF-1 as a key regulatory protein in many important and diverse pathways like embryonic stem cell pluripotency, stress responses and development. [1][2][3][4] Importantly, the discovery that gene-encoding HCF-1 is over-expressed in tumors, and this over-expression is a marker that predicts poor prognosis in cancer treatment proves that the functions of HCF-1 are more complex than previously appreciated. 5…”