S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component.
We have isolated and functionally characterized a multicomponent Oct-1 coactivator, OCA-S which is essential for S phase-dependent histone H2B transcription. The p38 component of OCA-S binds directly to Oct-1, exhibits potent transactivation potential, is selectively recruited to the H2B promoter in S phase, and is essential for S phase-specific H2B transcription in vivo and in vitro. Surprisingly, p38 represents a nuclear form of glyceraldehyde-3-phosphate dehydrogenase, and binding to Oct-1, as well as OCA-S function, is stimulated by NAD(+) but inhibited by NADH. OCA-S also interacts with NPAT, a cyclin E/cdk2 substrate that is broadly involved in histone gene transcription. These studies thus link the H2B transcriptional machinery to cell cycle regulators, and possibly to cellular metabolic state (redox status), and set the stage for studies of the underlying mechanisms and the basis for coordinated histone gene expression and coupling to DNA replication.
Zheng
Lei
L
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Roeder
Robert G
RG
Luo
Yan
Y
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics*; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D006657:Histones; D051863:Host Cell Factor C1; C101693:NPAT protein, human; D009687:Nuclear Proteins; C477239:OCA-S protein, human; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D048051:p38 Mitogen-Activated Protein Kinases