RETRACTED ARTICLE: DDB1 and Cul4 are necessary for gene silencing and heterochromatin formation at pericentromeric regions in Neurospora

Abstract

The heterochromatin is marked with histone H3K9 methylation, the marker of heterochromatin, is recognized and then bound by HP1 protein to initiate heterochromatin assembly. In fission yeast, Rik1 and Cul4 are needed in coordination with the histone methyltransferase Clr4 for H3K9 methylation. This modification is essential for recruiting HP1/Swi6 to initiate heterochromatin formation at pericentromeric and mating-type regions. In Neurospora crassa, DDB1 and Cul4 interact with the histone methyltransferase DIM-5 to form a complex for DNA methylation. However, it is unknown whether the DDB1 protein participates in gene silencing and heterochromatin formation in multicellular organisms. In the present study, we found that ddb1, cul4, and dim-5 deletion strains exhibited sensitivity to anti-microtubule drugs and displayed high frequencies of lagging chromosomes, suggesting that these proteins are involved in the proper functioning of the centromeres and cell division. We also found that deletion of ddb1 and cul4 led to the expression of a reporter gene, bar, that was inserted at the pericentromeric region of Neurospora cenVII. This finding confirmed that DDB1 and Cul4 were required to maintain the repressive heterochromatin state. Our findings indicated that DDB1 and Cul4 were necessary for gene silencing and heterochromatin formation at pericentromeric regions in Neurospora.