title: Lysyl oxidase regulates MMTV promoter: indirect evidence of histone H1 involvement.
abstract: Lysyl oxidase (LOX) is the enzyme that facilitates the cross-linking of collagen and elastin, although other functions for this enzyme have been indicated. Of these other functions, we describe herein the ability of LOX to regulate several gene promoters, like collagen III, elastin, and cyclin D1. We have previously demonstrated a specific binding between LOX and histone H1, in vitro. Therefore, we investigated whether LOX would affect the mouse mammary tumor virus (MMTV) promoter and its glucocorticoid regulation, which depends on the phophorylation status of histone H1. Our results show that the over-expression of recombinant human LOX was able to trigger MMTV activity, both in the presence and absence of glucocorticoids. Moreover, we demonstrated that histone H1 from cells expressing recombinant LOX contained isodesmosine and desmosine, indicating specific lysyl-oxidase-dependent lysine modifications. Finally, we were able to co-immunoprecipitate the exogenous LOX and histone H1 from the LOX transfected cells. The data are compatible with a decreased positive charge of histone H1, owing to deamination by LOX of its lysine residues. This event would favor H1 detachment from the target DNA, and consequent opening of the MMTV promoter structure to the activating transcription factors. The presented data, therefore, suggest a possible histone-H1-dependent mechanism for  the modulation of MMTV promoter by LOX.
authors: Department of Nephrology, Institute G. Gaslini, Genova, Italy.
authors: Roberta
authors: R
authors: Oleggini
authors: Armando
authors: A
authors: Di Donato
mesh_terms: D000629:Aminopropionitrile / Q000494:pharmacology; D045744:Cell Line, Tumor; D003895:Desmosine / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007524:Isodesmosine / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D006657:Histones; D011994:Recombinant Proteins; D014157:Transcription Factors; D003895:Desmosine; D000629:Aminopropionitrile; D003907:Dexamethasone; D007524:Isodesmosine; D008156:Luciferases; D008249:Protein-Lysine 6-Oxidase