In C. elegans, the dosage compensation complex (DCC) equalizes X chromosome gene dosage between XO males and XX hermaphrodites by repressing X transcription by two-fold specifically in hermaphrodites. The DCC is comprised of proteins homologous to the condensin complex, and it localizes to the X chromosomes in hermaphrodites but not in males. The mechanism by which the DCC downregulates expression in XX animals remains unclear. A genome-wide map of 19 histone modifications in two developmental stages of C. elegans (Liu et al, 2011) showed that the monomethylation of histone H4 at lysine 20 (H4K20me1) is enriched on the X chromosome of XX embryos and L3 larvae. H4K20me1 is also associated with actively transcribed genes on all chromosomes. The X-enrichment of H4K20me1 suggests a possible role for this modification in dosage compensation. Here, we report that H4K20me1 is enriched on the X chromosomes of XX hermaphrodites, but not in XO males. Enrichment of H4K20me1 on the X occurs after the localization of the DCC to the X and depends on the DCC function. In mammals, PR-Set7 catalyzes monomethylation of H4K20. RNAi knockdown of set-1, the likely C. elegans ortholog of PR-Set7, results in synthetic lethality with a number of dosage compensation mutations. These results support a function for H4K20me1 in dosage compensation. The X chromosome is also silenced in the germline in a DCC-independent manner. We found that in the mitotically proliferating zone of the germline, H4K20me1 is abundant on all chromosomes, but as nuclei enter meiosis, H4K20me1 levels are globally reduced. In contrast to somatic nuclei, H4K20me1 is specifically absent from the X chromosome during the meiotic prophase. H4K20me1 was recently shown to be important for chromosome condensation in mammals (Oda et al, 2009), possibly by recruiting condensin II (Liu et al, 2010). Our data indicate that the condensin-like C. elegans DCC preferentially increases H4K20me1 levels on the active X-linked genes. One plausible model for the role of H4K20me1 in dosage compensation is that preferential increase of H4K20me1 to the X may result in further recruitment of condensins to lower access of the transcription machinery to active X-linked genes. Liu et al (2011) Genome Res. 21, 227-36. Oda et al (2009) Mol Cell Biol. 29, 2278-95. Liu et al (2010) Nature. 466(7305):508-12.

Authors: Ahringer, Julie, Dernburg, Abby, Dong, Yan, Dose, Andrea, Egelhofer, Thea, Ercan, Sevinc, Kotwaliwale, Chitra, Lang, Jackie, Lieb, Jason, Liu, Shirley, Liu, Tao, Rechtsteiner, Andreas, Strome, Susan, Vielle, Anne

Affiliations:
- HHMI, UC Berkeley
- The Gurdon Institute, University of Cambridge
- Dept of Biology, New York University
- Dept of MCDB, UC Santa Cruz
- Dept of Biology, University of North Carolina
- Dept of BCB, Harvard School of Public Health