biostudies-literatureVielle AHoward Hughes Medical InstituteNHGRI NIH HHSWellcome Truste1002933https://www.ebi.ac.uk/biostudies/studies/S-EPMC3441679biostudies-literatureUnknown8(9)The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and pPLoS geneticsH4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.PMC34416790920961-U01-HG004270054523U01 HG004270Ercan SLang JLieb JDDong YVielle ADose AStrome SAppert ADernburg AKimura HStempor PChen QBEgelhofer TAhringer JKotwaliwale CRechtsteiner AfalseH4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and p2012-01-01T00:00:00Z2012 Sep2026-05-02T09:02:51.921Z2026-04-07T17:53:15.733ZS-EPMC34416792302834810.1371/journal.pgen.1002933