Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Dec;26(24):9185-95.
doi: 10.1128/MCB.01529-06. Epub 2006 Oct 9.

Profile of histone lysine methylation across transcribed mammalian chromatin

Christopher R Vakoc  1 , Mira M Sachdeva, Hongxin Wang, Gerd A Blobel
Affiliations

Profile of histone lysine methylation across transcribed mammalian chromatin

Christopher R Vakoc et al. Mol Cell Biol. 2006 Dec.

Abstract

Complex patterns of histone lysine methylation encode distinct functions within chromatin. We previously reported that trimethylation of lysine 9 of histone H3 (H3K9) occurs at both silent heterochromatin and at the transcribed regions of active mammalian genes, suggesting that the extent of histone lysine methylation involved in mammalian gene activation is not completely defined. To identify additional sites of histone methylation that respond to mammalian gene activity, we describe here a comparative assessment of all six known positions of histone lysine methylation and relate them to gene transcription. Using several model loci, we observed high trimethylation of H3K4, H3K9, H3K36, and H3K79 in the transcribed region, consistent with previous findings. We identify H4K20 monomethylation, a modification previously linked with repression, as a mark of transcription elongation in mammalian cells. In contrast, H3K27 monomethylation, a modification enriched at pericentromeric heterochromatin, was observed broadly distributed throughout all euchromatic sites analyzed, with selective depletion in the vicinity of the transcription start sites at active genes. Together, these results underscore that similar to other described methyl-lysine modifications, H4K20 and H3K27 monomethylation are versatile and dynamic with respect to gene activity, suggesting the existence of novel site-specific methyltransferases and demethylases coupled to the transcription cycle.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
The human PABPC1 gene encompasses a 25-kilobase domain of highly transcribed chromatin. A) ChIP of total RNA polymerase II across the PABPC1 locus, at MYT1, and CD4. B) Results of panel A presented on a different scale. C) ChIP using antibodies against LEO1. IgG, immunoglobulin G.
FIG.2.
FIG.2.
Histone methylation signature generated by active mammalian gene transcription. ChIP performed across the PABPC1 locus. MYT1 (+0.5-kb region) or CD4 (+0.5-kb region) served as controls. All distances are relative to the site of transcription initiation. Histone lysine methylation was measured using the following antibodies: A) H3K4me3; B) H3K9me3; C) H3K27me1, me2, and me3; D) H3K36me3; E) H3K79me3; F) H4K20me1, me2, and me3. G) Total histone H3. IgG, immunoglobulin G.
FIG.2.
FIG.2.
Histone methylation signature generated by active mammalian gene transcription. ChIP performed across the PABPC1 locus. MYT1 (+0.5-kb region) or CD4 (+0.5-kb region) served as controls. All distances are relative to the site of transcription initiation. Histone lysine methylation was measured using the following antibodies: A) H3K4me3; B) H3K9me3; C) H3K27me1, me2, and me3; D) H3K36me3; E) H3K79me3; F) H4K20me1, me2, and me3. G) Total histone H3. IgG, immunoglobulin G.
FIG. 3.
FIG. 3.
H3K27 monomethylation is dynamically removed in the vicinity of the transcription start site upon gene activation and is restored upon gene repression. ChIP experiments performed in G1E cells before or after tamoxifen (OHT) treatment. A) H3K27me1 at the major β-globin (β-major) gene. B) H3K27me1 at the GATA-2 gene. C) Histone H3 density at the major β-globin gene. D) Histone H3 density at the GATA-2 gene. IgG, immunoglobulin G.
FIG. 4.
FIG. 4.
H4K20 monomethylation is a mark of transcription elongation. ChIP experiments performed in GATA-1-ER-expressing G1E cells before or after tamoxifen (OHT) treatment. A) H4K20me1 at the major β-globin (β-major) gene. B) H4K20me1 at the c-kit gene. C) H3K36me3 at the major β-globin gene. D) H3K36me3 at the c-kit gene. E) Histone H3 density at the major β-globin gene. F) Histone H3 density at the c-kit gene. IgG, immunoglobulin G.
FIG. 5.
FIG. 5.
H4K20 monomethylation is dependent on elongating Pol II. ChIP was performed with the indicated antibodies. Cells were not treated cells or treated with DRB (+DRB) for 3 hours.
FIG. 6.
FIG. 6.
Inverse correlation between H3K9 acetylation and H3K9 trimethylation at the PABPC1 gene. ChIP was performed with antibodies against acetyl-H3K9 and H3K9me3. Note that the acetyl-H3K9 antibody gives stronger signals and that the y axes are different for the two antibodies. IgG, immunoglobulin G.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bannister, A. J., R. Schneider, F. A. Myers, A. W. Thorne, C. Crane-Robinson, and T. Kouzarides. 2005. Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J. Biol. Chem. 280:17732-17736. - PubMed
    1. Beisel, C., A. Imhof, J. Greene, E. Kremmer, and F. Sauer. 2002. Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1. Nature 419:857-862. - PubMed
    1. Bernstein, B. E., M. Kamal, K. Lindblad-Toh, S. Bekiranov, D. K. Bailey, D. J. Huebert, S. McMahon, E. K. Karlsson, E. J. Kulbokas III, T. R. Gingeras, S. L. Schreiber, and E. S. Lander. 2005. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169-181. - PubMed
    1. Bernstein, B. E., T. S. Mikkelsen, X. Xie, M. Kamal, D. J. Huebert, J. Cuff, B. Fry, A. Meissner, M. Wernig, K. Plath, R. Jaenisch, A. Wagschal, R. Feil, S. L. Schreiber, and E. S. Lander. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315-326. - PubMed
    1. Boeger, H., J. Griesenbeck, J. S. Strattan, and R. D. Kornberg. 2003. Nucleosomes unfold completely at a transcriptionally active promoter. Mol. Cell 11:1587-1598. - PubMed

Publication types