Histone H4-lysine 20 monomethylation is increased in promoter and coding regions of active genes and correlates with hyperacetylation.
Methylation and acetylation of position-specific lysine residues in the N-terminal tail of histones H3 and H4 play an important role in regulating chromatin structure and function. In the case of H3-Lys(4), H3-Lys(9), H3-Lys(27), and H4-Lys(20), the degree of methylation was variable from the mono- to the di- or trimethylated state, each of which was presumed to be involved in the organization of chromatin and the activation or repression of genes. Here we investigated the interplay between histone H4-Lys(20) mono- and trim-ethylation and H4 acetylation at induced (beta-major/beta-minor glo-bin), repressed (c-myc), and silent (embryonic beta-globin) genes during in vitro differentiation of mouse erythroleukemia cells. By using chromatin immunoprecipitation, we found that the beta-major and beta-minor promoter and the beta-globin coding regions as well as the promoter and the transcribed exon 2 regions of the highly expressed c-myc gene were hyperacetylated and monomethylated at H4-Lys(20). Although activation of the beta-globin gene resulted in an increase in hyperacetylated, monomethylated H4, down-regulation of the c-myc gene did not cause a decrease in hyperacetylated, monomethylated H4-Lys(20), thus showing a stable pattern of histone modifications. Immunofluorescence microscopy studies revealed that monomethylated H4-Lys(20) mainly overlaps with RNA pol II-stained euchromatic regions, thus indicating an association with transcriptionally engaged chromatin. Our chromatin immunoprecipitation results demonstrated that in contrast to trimethylated H4-Lys(20), which was found to inversely correlate with H4 hyper-acetylation, H4-Lys(20) monomethylation is compatible with histone H4 hyperacetylation and correlates with the transcriptionally active or competent chromatin state.
Talasz
Heribert
H
Biocenter, Division of Clinical Biochemistry, Innsbruck Medical University, A-6020, Innsbruck, Austria. Heribert.Talasz@uibk.ac.at
Lindner
Herbert H
HH
Sarg
Bettina
B
Helliger
Wilfried
W
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D002853:Chromatography, Liquid; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015536:Down-Regulation; D005091:Exons; D005557:Formaldehyde / Q000494:pharmacology; D005914:Globins / Q000737:chemistry; D006570:Heterochromatin / Q000737:chemistry; D006657:Histones / Q000737:chemistry*; D047468:Immunoprecipitation; D058610:Isobutyrates; D008239:Lysine / Q000737:chemistry*; D008745:Methylation; D051379:Mice; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic
D002087:Butyrates; D002843:Chromatin; D003432:Cross-Linking Reagents; D006570:Heterochromatin; D006657:Histones; D058610:Isobutyrates; D016271:Proto-Oncogene Proteins c-myc; D005557:Formaldehyde; C020380:isobutyric acid; D005914:Globins; D008239:Lysine