Cascade of Distinct Histone Modifications during Collagenase Gene Activation

Abstract

Gene activation in eukaryotes requires chromatin remodeling, in part via histone modifications. To study the events at the promoter of a mitogen-inducible gene, we examined the induction of expression of the collagenase gene. It has been established that the collagenase gene can be activated by c-Jun and c-Fos and that the transcriptional coactivator p300 is involved in the activation. As expected, we found histone acetyltransferase activity at the collagenase promoter during activation. Interestingly, we also found histone methyltransferase and kinase activity. Strikingly, the first modification observed is methylation of histone H3 lysine 4, which correlates with the binding of the SET9 methyltransferase and the assembly of a complex consisting of c-Jun, c-Fos, TATA binding protein, and RNA polymerase II. The assembly of the preinitiation complex also shows an ordered binding of the acetyltransferase p300, the RSK2 kinase, and the SWI/SNF component Brg-1. Our results suggest that collagenase gene activation involves a dynamic recruitment of different factors and that in addition to acetylation, histone H3 lysine 4 di-and trimethylation and histone H3 serine 10 phosphorylation are important steps in the activation of this gene.In eukaryotic cells, genomic DNA is packaged into nucleosomes, the basic unit of chromatin structure. The packaging of DNA into chromatin has a repressive effect on gene expression, and therefore, reconfiguration of chromatin has been postulated as mandatory for transcriptional initiation (24,34,45). One of the central questions in this process is how RNA polymerase and associated proteins gain access to chromatin templates. Increasing evidence indicates that gene expression is regulated by means of facilitating access of DNA-binding factors to DNA via chromatin-remodeling factors and covalent histone modifications (14).The major chromatin-remodeling factors are the SWI/SNF ATP-dependent remodeling complexes. Upon recruitment, these complexes are thought to alter the structure of the promoter-bound nucleosome in an ATP-dependent manner (34).The covalent-histone modifications are brought about by proteins that, upon recruitment, can phosphorylate, acetylate, and methylate histone tails (5, 41). The best-studied histone modification involved in transcriptional activation is acetylation. Levels of acetylated histones H3 and H4 have been correlated with the transcription status of many genes: transcriptionally active euchromatin regions of the genome are often associated with hyperacetylated histones, whereas transcriptionally silent regions are associated with hypoacetylated histones (17). In vivo, the steady-state levels of histone acetylation are maintained by the balance of the opposing histone acetyltransferase (HAT) and histone deacetylase activities, and these enzymes are associated with gene activation and repression, respectively (21, 44). Besides acetylation, phosphorylation of histone H3 on serine 10 is also associated with gene activation. Phosphorylation, mediated via ERK or p38 ...

SWI/SNF Binding to the HO Promoter Requires Histone Acetylation and Stimulates TATA-Binding Protein Recruitment

“…We find that the Gcn5 histone acetyltransferase activity is required for SWI/SNF to stably associate with the HO promoter, at least in the presence of the Ash1 negative regulator. Sequential recruitment of transcription factors has also been seen at other genes, including the human beta interferon, ␣1 antitrypsin, collagenase, and PPAR␥2 genes (2,58,73,77), and for each of these promoters, binding of a Gcn5-like histone acetyltransferase precedes SWI/SNF binding (2,58,73,77). It has also been shown that histone acetylation precedes SWI/SNF bind- ing at the myogenin promoter (29) and that a gcn5 mutation reduces the rate at which SWI/SNF is recruited to the SUC2 promoter following induction (35).…”

“…Thereafter, Mediator binds to the TATA region, dependent on the SBF factor. Activation of the Cdc28 cyclin-dependent kinase is required for binding of RNA polymerase, TFIIB, and TFIIH at the HO TATA (24).Ordered recruitment of transcription factors has also been seen at other promoters (for a review, see reference 23), including the human beta interferon, ␣1 antitrypsin, collagenase, and PPAR␥2 promoters (2,58,73,77). For example, at the beta interferon promoter, binding of sequence-specific factors results in the sequential recruitment of the Gcn5 complex, followed by the CBP-RNA Pol II complex and then the SWI/SNF complex (2).…”

Histone H3 Lysine 4 Dimethylation Signals the Transcriptional Competence of the Adiponectin Promoter in Preadipocytes

“…Similarly, at the inducible collagenase promoter, which has been shown to be rapidly dimethylated at H3-K4 following mitogen stimulation (48), preincubation with 2 mM MTA blocked the induction of the gene. Our results are in accordance with these data and argue for a positive role of H3-K4 dimethylation in regulating transcription of adipogenic genes and ultimately, the differentiation process.…”

Extracellular Signals Regulate Rapid Coactivator Recruitment at AP-1 Sites by Altered Phosphorylation of both CREB Binding Protein and c-jun

“…PCAF can associate with CBP and with nuclear receptors independently of CBP (5). p300/CBP has been shown to activate the collagenase type I gene via AP-1 sites (24). CBP also was required for the activation of RA responsive genes, and inhibition of AP-1 activity by RA was attributed to RAR competition for limiting amounts of CBP.…”