Skip to main content
SpringerLink
Log in

Conservation and divergence of the histone H2B monoubiquitination pathway from yeast to humans and plants

  • Review
  • Published:
Frontiers in Biology

Abstract

Histone ubiquitination plays a critical role in the regulation of transcription, and histone H2B monoubiquitination (H2Bub1) is mainly associated with transcriptional activation. Recent studies in yeast, humans, and Arabidopsis have revealed the conservation of chromatin modification via H2Bub1 during evolution. Rad6-Bre1 and their homologs are responsible for H2B monoubiquitination in diverse eukaryotic organisms, and the PAF complex is required for H2Bub1 to proceed. H2Bub1 is involved in many developmental processes in yeast, humans, and Arabidopsis, and it activates gene transcription by regulating the H3K4 methylation state. Notably, the level of H3K4 methylation is entirely dependent on H2Bub1 in yeast and humans, whereas the H3K4 methylation level of only a small number of genes in Arabidopsis is dependent on H2Bub1. In this review, we summarize the enzymes involved in H2B monoubiquitination and deubiquitination, and discuss the biologic functions of H2Bub1 in different organisms. In addition, we focus on recent advances in our understanding of the molecular mechanisms that enable H2Bub1 to perform its function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Briggs S D, Xiao T, Sun Z W, Caldwell J A, Shabanowitz J, Hunt D F, Allis C D, Strahl B D (2002). Gene silencing: trans-histone regulatory pathway in chromatin. Nature, 418(6897): 498

    Article  PubMed  CAS  Google Scholar 

  • Cao Y, Dai Y, Cui S J, Ma L G (2008). Histone H2B monoubiquitination in the chromatin of FLOWERING LOCUS C regulates flowering time in Arabidopsis. Plant Cell, 20: 2586–2602

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekharan M B, Huang F, Chen Y C, Sun Z W (2010b). Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination. Mol Cell Biol, 30(13): 3216–3232

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekharan M B, Huang F, Sun Z W (2009). Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability. Proc Natl Acad Sci USA, 106(39): 16686–16691

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekharan M B, Huang F, Sun Z W (2010a). Histone H2B ubiquitination and beyond: Regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation. Epigenetics, 5(6): 460–468

    Article  PubMed  CAS  Google Scholar 

  • Daniel J A, Torok M S, Sun Z W, Schieltz D, Allis C D, Yates J R 3rd, Grant P A (2004). Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription. J Biol Chem, 279(3): 1867–1871

    Article  PubMed  CAS  Google Scholar 

  • Dhawan R, Luo H, Foerster A M, Abuqamar S, Du H N, Briggs S D, Scheid O M, Mengiste T (2009). HISTONE MONOUBIQUITINATION1 interacts with a subunit of the mediator complex and regulates defense against necrotrophic fungal pathogens in Arabidopsis. Plant Cell, 21(3): 1000–1019

    Article  PubMed  CAS  Google Scholar 

  • Dover J, Schneider J, Tawiah-Boateng M A, Wood A, Dean K, Johnston M, Shilatifard A (2002). Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6. J Biol Chem, 277(32): 28368–28371

    Article  PubMed  CAS  Google Scholar 

  • Emre N C, Ingvarsdottir K, Wyce A, Wood A, Krogan N J, Henry K W, Li K, Marmorstein R, Greenblatt J F, Shilatifard A, Berger S L (2005). Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing. Mol Cell, 17(4): 585–594

    Article  PubMed  CAS  Google Scholar 

  • Espinosa J M (2008). Histone H2B ubiquitination: the cancer connection. Genes Dev, 22(20): 2743–2749

    Article  PubMed  CAS  Google Scholar 

  • Ezhkova E, Tansey W P (2004). Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. Mol Cell, 13(3): 435–442

    Article  PubMed  CAS  Google Scholar 

  • Fleming A B, Kao C F, Hillyer C, Pikaart M, Osley M A (2008). H2B ubiquitylation plays a role in nucleosome dynamics during transcription elongation. Mol Cell, 31(1): 57–66

    Article  PubMed  CAS  Google Scholar 

  • Fleury D, Himanen K, Cnops G, Nelissen H, Boccardi T M, Maere S, Beemster G T S, Neyt P, Anami S, Robles P, Micol J L, Inzé D, Van Lijsebettens M (2007). The Arabidopsis thaliana homolog of yeast BRE1 has a function in cell cycle regulation during early leaf and root growth. Plant Cell, 19(2): 417–432

    Article  PubMed  CAS  Google Scholar 

  • Gardner R G, Nelson Z W, Gottschling D E (2005). Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: distinct roles in telomeric silencing and general chromatin. Mol Cell Biol, 25(14): 6123–6139

    Article  PubMed  CAS  Google Scholar 

  • Goldknopf I L, Taylor C W, Baum R M, Yeoman L C, Olson M O, Prestayko A W, Busch H (1975). Isolation and characterization of protein A24, a “histone-like” non-histone chromosomal protein. J Biol Chem, 250(18): 7182–7187

    PubMed  CAS  Google Scholar 

  • Gu X, Jiang D, Wang Y, Bachmair A, He Y (2009). Repression of the floral transition via histone H2B monoubiquitination. Plant J, 57(3): 522–533

    Article  PubMed  CAS  Google Scholar 

  • Hartzog G A, Quan T K (2008). Just the FACTs: histone H2B ubiquitylation and nucleosome dynamics. Mol Cell, 31(1): 2–4

    Article  PubMed  CAS  Google Scholar 

  • Henry KW, Wyce A, Lo WS, Duggan L J, Emre N C T, Kao C F, Pillus L, Shilatifard A, Osley M A, Berger S L (2003). Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev, 17(21): 2648–2663

    Article  PubMed  CAS  Google Scholar 

  • Hwang WW, Venkatasubrahmanyam S, Ianculescu A G, Tong A, Boone C, Madhani H D (2003). A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell, 11(1): 261–266

    Article  PubMed  CAS  Google Scholar 

  • Ingvarsdottir K, Krogan N J, Emre N C, Wyce A, Thompson N J, Emili A, Hughes T R, Greenblatt J F, Berger S L (2005). H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex. Mol Cell Biol, 25(3): 1162–1172

    Article  PubMed  CAS  Google Scholar 

  • Jenuwein T, Allis C D (2001). Translating the histone code. Science, 293(5532): 1074–1080

    Article  PubMed  CAS  Google Scholar 

  • Kao C F, Hillyer C, Tsukuda T, Henry K, Berger S, Osley M A (2004). Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev, 18(2): 184–195

    Article  PubMed  CAS  Google Scholar 

  • Kim J, Guermah M, McGinty R K, Lee J S, Tang Z, Milne T A, Shilatifard A, Muir T W, Roeder R G (2009). RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell, 137(3): 459–471

    Article  PubMed  CAS  Google Scholar 

  • Kim J, Hake S B, Roeder R G (2005). The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol Cell, 20(5): 759–770

    Article  PubMed  CAS  Google Scholar 

  • Kornberg R D, Lorch Y (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell, 98(3): 285–294

    Article  PubMed  CAS  Google Scholar 

  • Kouzarides T (2007). Chromatin modifications and their function. Cell, 128(4): 693–705

    Article  PubMed  CAS  Google Scholar 

  • Krogan N J, Dover J, Wood A, Schneider J, Heidt J, Boateng M A, Dean K, Ryan O W, Golshani A, Johnston M, Greenblatt J F, Shilatifard A (2003). The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell, 11(3): 721–729

    Article  PubMed  CAS  Google Scholar 

  • Laribee R N, Fuchs S M, Strahl B D (2007a). H2B ubiquitylation in transcriptional control: a FACT-finding mission. Genes Dev, 21(7): 737–743

    Article  PubMed  CAS  Google Scholar 

  • Laribee R N, Shibata Y, Mersman D P, Collins S R, Kemmeren P, Roguev A, Weissman J S, Briggs S D, Krogan N J, Strahl B D (2007b). CCR4/NOT complex associates with the proteasome and regulates histone methylation. Proc Natl Acad Sci USA, 104(14): 5836–5841

    Article  PubMed  CAS  Google Scholar 

  • Lee J S, Shukla A, Schneider J, Swanson S K, Washburn M P, Florens L, Bhaumik S R, Shilatifard A (2007). Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS. Cell, 131(6): 1084–1096

    Article  PubMed  CAS  Google Scholar 

  • Lee K K, Florens L, Swanson S K, Washburn MP, Workman J L (2005). The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex. Mol Cell Biol, 25(3): 1173–1182

    Article  PubMed  CAS  Google Scholar 

  • Li B, Carey M, Workman J L (2007). The role of chromatin during transcription. Cell, 128(4): 707–719

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Koornneef M, Soppe W J J (2007). The absence of histone H2B monoubiquitination in the Arabidopsis hub1 (rdo4) mutant reveals a role for chromatin remodeling in seed dormancy. Plant Cell, 19(2): 433–444

    Article  PubMed  Google Scholar 

  • Lolas I B, Himanen K, Grønlund J T, Lynggaard C, Houben A, Melzer M, Van Lijsebettens M, Grasser K D (2010). The transcript elongation factor FACT affects Arabidopsis vegetative and reproductive development and genetically interacts with HUB1/2. Plant J, 61(4): 686–697

    Article  PubMed  CAS  Google Scholar 

  • Luger K, Mäder A W, Richmond R K, Sargent D F, Richmond T J (1997). Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature, 389(6648): 251–260

    Article  PubMed  CAS  Google Scholar 

  • Minsky N, Shema E, Field Y, Schuster M, Segal E, Oren M (2008). Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat Cell Biol, 10(4): 483–488

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi S, Lee J S, Gardner K E, Gardner J M, Takahashi Y H, Chandrasekharan M B, Sun Z W, Osley M A, Strahl B D, Jaspersen S L, Shilatifard A (2009). Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J Cell Biol, 186(3): 371–377

    Article  PubMed  CAS  Google Scholar 

  • Ng H H, Dole S, Struhl K (2003). The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B. J Biol Chem, 278(36): 33625–33628

    Article  PubMed  CAS  Google Scholar 

  • Oh S, Zhang H, Ludwig P, van Nocker S (2004). A mechanism related to the yeast transcriptional regulator Paf1c is required for expression of the Arabidopsis FLC/MAF MADS box gene family. Plant Cell, 16(11): 2940–2953

    Article  PubMed  CAS  Google Scholar 

  • Osley M A (2004). H2B ubiquitylation: the end is in sight. Biochim Biophys Acta, 1677(1–3): 74–78

    PubMed  CAS  Google Scholar 

  • Osley M A (2006). Regulation of histone H2A and H2B ubiquitylation. Brief Funct Genomics Proteomics, 5(3): 179–189

    Article  CAS  Google Scholar 

  • Osley M A, Fleming A B, Kao C F (2006). Histone ubiquitylation and the regulation of transcription. Results Probl Cell Differ, 41: 47–75

    Article  PubMed  CAS  Google Scholar 

  • Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, Reinberg D (2006). Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell, 125(4): 703–717

    Article  PubMed  CAS  Google Scholar 

  • Pfluger J, Wagner D (2007). Histone modifications and dynamic regulation of genome accessibility in plants. Curr Opin Plant Biol, 10(6): 645–652

    Article  PubMed  CAS  Google Scholar 

  • Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman R D, Eick D, Aylon Y, Oren M, Johnsen S A (2009). CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing. EMBO Rep, 10(8): 894–900

    Article  PubMed  CAS  Google Scholar 

  • Robzyk K, Recht J, Osley M A (2000). Rad6-dependent ubiquitination of histone H2B in yeast. Science, 287(5452): 501–504

    Article  PubMed  CAS  Google Scholar 

  • Schmitz R J, Tamada Y, Doyle M R, Zhang X, Amasino R M (2009). Histone H2B deubiquitination is required for transcriptional activation of FLOWERING LOCUS C and for proper control of flowering in Arabidopsis. Plant Physiol, 149(2): 1196–1204

    Article  PubMed  CAS  Google Scholar 

  • Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, Raver-Shapira N, Minsky N, Pirngruber J, Tarcic G, Hublarova P, Moyal L, Gana-Weisz M, Shiloh Y, Yarden Y, Johnsen S A, Vojtesek B, Berger S L, Oren M (2008). The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev, 22(19): 2664–2676

    Article  PubMed  CAS  Google Scholar 

  • Shukla A, Bhaumik S R (2007). H2B-K123 ubiquitination stimulates RNAPII elongation independent of H3-K4 methylation. Biochem Biophys Res Commun, 359(2): 214–220

    Article  PubMed  CAS  Google Scholar 

  • Sridhar V V, Kapoor A, Zhang K, Zhu J, Zhou T, Hasegawa P M, Bressan R A, Zhu J K (2007). Control of DNA methylation and heterochromatic silencing by histone H2B deubiquitination. Nature, 447(7145): 735–738

    Article  PubMed  CAS  Google Scholar 

  • Sun Z W, Allis C D (2002). Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature, 418(6893): 104–108

    Article  PubMed  CAS  Google Scholar 

  • Tanny J C, Erdjument-Bromage H, Tempst P, Allis C D (2007). Ubiquitylation of histone H2B controls RNA polymerase II transcription elongation independently of histone H3 methylation. Genes Dev, 21(7): 835–847

    Article  PubMed  CAS  Google Scholar 

  • Turner B M (2002). Cellular memory and the histone code. Cell, 111(3): 285–291

    Article  PubMed  CAS  Google Scholar 

  • Weake V M, Workman J L (2008). Histone ubiquitination: triggering gene activity. Mol Cell, 29(6): 653–663

    Article  PubMed  CAS  Google Scholar 

  • West M H, Bonner W M (1980). Histone 2B can be modified by the attachment of ubiquitin. Nucleic Acids Res, 8(20): 4671–4680

    Article  PubMed  CAS  Google Scholar 

  • Wood A, Krogan N J, Dover J, Schneider J, Heidt J, Boateng M A, Dean K, Golshani A, Zhang Y, Greenblatt J F, Johnston M, Shilatifard A (2003a). Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell, 11(1): 267–274

    Article  PubMed  CAS  Google Scholar 

  • Wood A, Schneider J, Dover J, Johnston M, Shilatifard A (2003b). The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. J Biol Chem, 278(37): 34739–34742

    Article  PubMed  CAS  Google Scholar 

  • Wyce A, Henry K W, Berger S L (2004). H2B ubiquitylation and deubiquitylation in gene activation. Novartis Found Symp, 259: 63–73, discussion 73–77, 163–169

    Article  PubMed  CAS  Google Scholar 

  • Wyce A, Xiao T, Whelan K A, Kosman C, Walter W, Eick D, Hughes T R, Krogan N J, Strahl B D, Berger S L (2007). H2B ubiquitylation acts as a barrier to Ctk1 nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex. Mol Cell, 27(2): 275–288

    Article  PubMed  CAS  Google Scholar 

  • Xiao T, Kao C F, Krogan N J, Sun Z W, Greenblatt J F, Osley M A, Strahl B D (2005). Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol, 25(2): 637–651

    Article  PubMed  CAS  Google Scholar 

  • Xu L, Ménard R, Berr A, Fuchs J, Cognat V, Meyer D, Shen W H (2009). The E2 ubiquitin-conjugating enzymes, AtUBC1 and AtUBC2, play redundant roles and are involved in activation of FLC expression and repression of flowering in Arabidopsis thaliana. Plant J, 57(2): 279–288

    Article  PubMed  CAS  Google Scholar 

  • Zhang X Y, Varthi M, Sykes S M, Phillips C, Warzecha C, Zhu W, Wyce A, Thorne A W, Berger S L, McMahon S B (2008). The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell, 29(1): 102–111

    Article  PubMed  Google Scholar 

  • Zhang Y (2003). Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev, 17(22): 2733–2740

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Lang G, Ito S, Bonnet J, Metzger E, Sawatsubashi S, Suzuki E, Le Guezennec X, Stunnenberg H G, Krasnov A, Georgieva S G, Schüle R, Takeyama K, Kato S, Tora L, Devys D (2008). A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell, 29(1): 92–101

    Article  PubMed  CAS  Google Scholar 

  • Zhu B, Mandal S S, Pham A D, Zheng Y, Erdjument-Bromage H, Batra S K, Tempst P, Reinberg D (2005a). The human PAF complex coordinates transcription with events downstream of RNA synthesis. Genes Dev, 19(14): 1668–1673

    Article  PubMed  CAS  Google Scholar 

  • Zhu B, Zheng Y, Pham A D, Mandal S S, Erdjument-Bromage H, Tempst P, Reinberg D (2005b). Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell, 20(4): 601–611

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Molecular Cell Biology, College of Life Science, Hebei Normal University, Shijiazhuang, 050016, China

    Ying Cao & Ligeng Ma

Authors
  1. Ying Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ligeng Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ligeng Ma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cao, Y., Ma, L. Conservation and divergence of the histone H2B monoubiquitination pathway from yeast to humans and plants. Front. Biol. 6, 109–117 (2011). https://doi.org/10.1007/s11515-011-1000-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-011-1000-6

Keywords

Search

Navigation