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H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.
PLoS Genet. 2012 Sep; 8(9):e1002933.PG

Abstract

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 provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction.

Authors+Show Affiliations

The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23028348

Citation

Vielle, Anne, et al. "H4K20me1 Contributes to Downregulation of X-linked Genes for C. Elegans Dosage Compensation." PLoS Genetics, vol. 8, no. 9, 2012, pp. e1002933.
Vielle A, Lang J, Dong Y, et al. H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genet. 2012;8(9):e1002933.
Vielle, A., Lang, J., Dong, Y., Ercan, S., Kotwaliwale, C., Rechtsteiner, A., Appert, A., Chen, Q. B., Dose, A., Egelhofer, T., Kimura, H., Stempor, P., Dernburg, A., Lieb, J. D., Strome, S., & Ahringer, J. (2012). H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genetics, 8(9), e1002933. https://doi.org/10.1371/journal.pgen.1002933
Vielle A, et al. H4K20me1 Contributes to Downregulation of X-linked Genes for C. Elegans Dosage Compensation. PLoS Genet. 2012;8(9):e1002933. PubMed PMID: 23028348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. AU - Vielle,Anne, AU - Lang,Jackie, AU - Dong,Yan, AU - Ercan,Sevinc, AU - Kotwaliwale,Chitra, AU - Rechtsteiner,Andreas, AU - Appert,Alex, AU - Chen,Q Brent, AU - Dose,Andrea, AU - Egelhofer,Thea, AU - Kimura,Hiroshi, AU - Stempor,Przemyslaw, AU - Dernburg,Abby, AU - Lieb,Jason D, AU - Strome,Susan, AU - Ahringer,Julie, Y1 - 2012/09/13/ PY - 2012/03/20/received PY - 2012/07/02/accepted PY - 2012/10/3/entrez PY - 2012/10/3/pubmed PY - 2013/1/5/medline SP - e1002933 EP - e1002933 JF - PLoS genetics JO - PLoS Genet. VL - 8 IS - 9 N2 - 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 provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/23028348/H4K20me1_contributes_to_downregulation_of_X_linked_genes_for_C__elegans_dosage_compensation_ L2 - http://dx.plos.org/10.1371/journal.pgen.1002933 DB - PRIME DP - Unbound Medicine ER -