Article thumbnail

USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation

By Ryan Draker, Elizabeth Sarcinella and Peter Cheung

Abstract

H2A.Z, a variant of H2A, is found at the promoters of inducible genes in both yeast and higher eukaryotes. However, its role in transcriptional regulation is complex since it has been reported to function both as a repressor and activator. We have previously found that mono-ubiquitylation of H2A.Z is linked to transcriptional silencing. Here, we provide new evidence linking H2A.Z deubiquitylation to transcription activation. We found that H2A.Z and ubiquitin-specific protease 10 (USP10) are each required for transcriptional activation of the androgen receptor (AR)-regulated PSA and KLK3 genes. USP10 directly deubiquitylates H2A.Z in vitro and in vivo, and reducing USP10 expression in prostate cancer cells results in elevated steady-state levels of mono-ubiquitylated H2A.Z (H2A.Zub1). Moreover, knockdown of USP10 ablates hormone-induced deubiquitylation of chromatin proteins at the AR-regulated genes. Finally, by sequential ChIP assays, we found that H2A.Zub1 is enriched at the PSA and KLK3 regulatory regions, and loss of H2A.Zub1 is associated with transcriptional activation of these genes. Together, these data provide novel insights into how H2A.Z ubiquitylation/deubiquitylation and USP10 function in AR-regulated gene expression

Topics: Gene Regulation, Chromatin and Epigenetics
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:3089478
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2007). A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.
  2. (1999). A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division.
  3. (1997). A signature motif in transcriptional co-activators mediates binding to nuclear receptors.
  4. (2008). A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing.
  5. (2006). Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast.
  6. (2009). Acetylation of vertebrate H2A.Z and its effect on the structure of the nucleosome.
  7. (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
  8. (2007). Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex.
  9. (2009). Breaking the chains: structure and function of the deubiquitinases.
  10. (2006). Characterization of histone H2A and H2B variants and their post-translational modifications by mass spectrometry.
  11. (2009). Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates.
  12. (2001). Characterization of the stability and folding of H2A.Z chromatin particles: implications for transcriptional activation.
  13. (2003). Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin.
  14. (2006). Degradation and beyond: control of androgen receptor activity by the proteasome system.
  15. (2008). Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation.
  16. (1998). DNA damage activates p53 through a phosphorylation-acetylation cascade.
  17. (2007). Evidence based selection of housekeeping genes.
  18. (2005). Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/ basal promoters for activation through histone loss.
  19. (2003). H2A.Z has a function reminiscent of an activator required for preferential binding to intergenic DNA.
  20. (2001). H2A.Z is required for global chromatin integrity and for recruitment of RNA polymerase II under specific conditions.
  21. (2009). Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs.
  22. (2009). Histone H2A.Z is essential for estrogen receptor signaling.
  23. (2000). Histone H2A.Z regulats transcription and is partially redundant with nucleosome remodeling complexes.
  24. (2005). Histone variant H2A.Z marks the 50 ends of both active and inactive genes in euchromatin.
  25. (2010). Histone variant H2A.Z regulates centromere silencing and chromosome segregation in fission yeast.
  26. (2001). hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.
  27. (2007). Human USP3 is a chromatin modifier required for S phase progression and genome stability.
  28. (2008). Interaction of the glucocorticoid receptor with the chromatin landscape.
  29. (2006). JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor.
  30. (2009). Labile H3.3+H2A.Z nucleosomes mark ‘nucleosome-free regions’.
  31. (2005). LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription.
  32. (2007). Monoubiquitylation of H2A.Z distinguishes its association with euchromatin or facultative heterochromatin.
  33. (2007). Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.
  34. (1988). Nuclease hypersensitive sites in chromatin.
  35. (2007). Nucleosome stability mediated by histone variants
  36. (2007). p53 is regulated by the lysine demethylase LSD1.
  37. (1999). p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage.
  38. (2005). Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling.
  39. (2006). Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes.
  40. (2006). Quantitative proteomic analysis of post-translational modifications of human histones.
  41. (2001). Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease.
  42. (2007). Regulation of cell cycle 3540
  43. (2009). Regulation of gene expression and cellular proliferation by histone H2A.Z.
  44. (2006). Reuniting the contrasting functions of H2A.Z.
  45. (2004). RNA interference demonstrates a novel role for H2A.Z in chromosome segregation.
  46. (2003). SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1.
  47. (2006). Telomeric heterochromatin boundaries require NuA4-dependent acetylation of histone variant H2A.Z in Saccharomyces cerevisiae.
  48. (2010). The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells.
  49. (2009). The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells.
  50. (2009). The evolutionary differentiation of two histone H2A.Z variants in chordates (H2A.Z-1 and H2A.Z-2) is mediated by a stepwise mutation process that affects three amino acid residues.
  51. (2005). The H2A.Z/H2B dimer is unstable compared to the dimer containing the major H2A isoform.
  52. (2008). The many faces of ubiquitinated histone H2A: insights from the DUBs.
  53. (2005). The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken.
  54. (2005). The ubiquitin-specific protease USP10 modulates androgen receptor function.
  55. (2005). Transcription-induced chromatin remodeling at the c-myc gene involves the local exchange of histone H2A.Z.
  56. (2009). Transcriptional and epigenetic functions of histone variant H2A.Z.
  57. (2010). USP10 regulates p53 localization and stability by deubiquitinating p53.
  58. (2005). Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning.
  59. (2008). Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3.