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PMID:16307923

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Citation

Zhu, B, Zheng, Y, Pham, AD, Mandal, SS, Erdjument-Bromage, H, Tempst, P and Reinberg, D (2005) Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol. Cell 20:601-11

Abstract

In yeast, histone H2B monoubiquitination is a cotranscriptional event regulating histone H3 methylation at lysines 4 and 79. However, mammalian H2B monoubiquitination remains poorly understood. We report that in humans, the 600 kDa RNF20/40 complex is the E3 ligase and UbcH6 is the ubiquitin E2-conjugating enzyme for H2B-Lys120 monoubiquitination. RNF20 and RNF40 are both homologs of Bre1, the E3 ligase in the yeast case. UbcH6 physically interacts with RNF20/40 and with the hPAF complex. Formation of a trimeric complex with hPAF stimulates H2B monoubiquitination activity in vitro. Accordingly, UbcH6, RNF20/40, and the hPAF complex are recruited to transcriptionally active genes in vivo. RNF20 overexpression leads to elevated H2B monoubiquitination, subsequently higher levels of methylation at H3 lysines 4 and 79, and stimulation of HOX gene expression. In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression.

Links

PubMed Online version:10.1016/j.molcel.2005.09.025

Keywords

DNA Methylation; Gene Expression Regulation/physiology; HeLa Cells; Histones/metabolism; Homeodomain Proteins/antagonists & inhibitors; Homeodomain Proteins/biosynthesis; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Nuclear Proteins/antagonists & inhibitors; Nuclear Proteins/genetics; Nuclear Proteins/physiology; RNA Interference; RNA Polymerase II/physiology; Ubiquitin/metabolism; Ubiquitin-Conjugating Enzymes/physiology; Ubiquitin-Protein Ligases/antagonists & inhibitors; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/isolation & purification; Ubiquitin-Protein Ligases/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BRE1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5VTR2

F

Seeded From UniProt

complete

HUMAN:BRE1B

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRE1B

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRE1B

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRE1B

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5VTR2

F

Seeded From UniProt

complete

HUMAN:BRE1B

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRE1B

contributes_to

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UB2E1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5VTR2

F

Seeded From UniProt

complete

HUMAN:UB2E1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8N7H5

F

Seeded From UniProt

complete

HUMAN:BRE1A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75150

F

Seeded From UniProt

complete

HUMAN:BRE1A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51965

F

Seeded From UniProt

complete

HUMAN:BRE1A

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRE1A

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRE1A

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRE1A

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75150

F

Seeded From UniProt

complete

HUMAN:BRE1A

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRE1A

contributes_to

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CDC73

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDC73

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDC73

part_of

GO:0016593: Cdc73/Paf1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTR9

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CTR9

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CTR9

part_of

GO:0016593: Cdc73/Paf1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PAF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51965

F

Seeded From UniProt

complete

HUMAN:UB2E1

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2E1

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2E1

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UB2E1

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PAF1

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAF1

part_of

GO:0016593: Cdc73/Paf1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PAF1

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEO1

involved_in

GO:0033523: histone H2B ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEO1

part_of

GO:0016593: Cdc73/Paf1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LEO1

involved_in

GO:0010390: histone monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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