A Trans-tail Histone Code Defined by Monomethylated H4 Lys-20 and H3 Lys-9 Demarcates Distinct Regions of Silent Chromatin

Abstract

The specific post-translational modifications of the histone proteins are associated with specific DNA-templated processes, such as transcriptional activation or repression. To investigate the biological role(s) of histone H4 lysine 20 (H4 Lys-20) methylation, we created a novel panel of antibodies that specifically detected mono-, di-, or trimethylated H4 Lys-20. We report that the different methylated forms of H4 Lys-20 are compartmentalized within visually distinct, transcriptionally silent regions in the mammalian nucleus. Interestingly, direct comparison of methylated H4 Lys-20 with the different methylated states of histone H3 lysine 9 (H3 Lys-9) revealed significant overlap and exclusion between the specific groups of methyl modifications. Trimethylated H4 Lys-20 and H3 Lys-9 were both selectively enriched within pericentric heterochromatin. Similarly, monomethylated H4 Lys-20 and H3 Lys-9 partitioned together and the dimethylated forms partitioned together within the chromosome arms; however, the mono- and dimethylated modifications were virtually exclusive. These findings strongly suggest that the combinatorial presence or absence of the different methylated states of H4 Lys-20 and H3 Lys-9 define particular types of silent chromatin. Consistent with this, detailed analysis of monomethylated H4 Lys-20 and H3 Lys-9 revealed that both were preferentially and selectively enriched within the same nucleosome particle in vivo. Collectively, these findings define a novel trans-tail histone code involving monomethylated H4 Lys-20 and H3 Lys-9 that act cooperatively to mark distinct regions of silent chromatin within the mammalian epigenome. The specific post-translational modifications of the histone proteins are associated with specific DNA-templated processes, such as transcriptional activation or repression. To investigate the biological role(s) of histone H4 lysine 20 (H4 Lys-20) methylation, we created a novel panel of antibodies that specifically detected mono-, di-, or trimethylated H4 Lys-20. We report that the different methylated forms of H4 Lys-20 are compartmentalized within visually distinct, transcriptionally silent regions in the mammalian nucleus. Interestingly, direct comparison of methylated H4 Lys-20 with the different methylated states of histone H3 lysine 9 (H3 Lys-9) revealed significant overlap and exclusion between the specific groups of methyl modifications. Trimethylated H4 Lys-20 and H3 Lys-9 were both selectively enriched within pericentric heterochromatin. Similarly, monomethylated H4 Lys-20 and H3 Lys-9 partitioned together and the dimethylated forms partitioned together within the chromosome arms; however, the mono- and dimethylated modifications were virtually exclusive. These findings strongly suggest that the combinatorial presence or absence of the different methylated states of H4 Lys-20 and H3 Lys-9 define particular types of silent chromatin. Consistent with this, detailed analysis of monomethylated H4 Lys-20 and H3 Lys-9 revealed that both were preferentially and selectively enriched within the same nucleosome particle in vivo. Collectively, these findings define a novel trans-tail histone code involving monomethylated H4 Lys-20 and H3 Lys-9 that act cooperatively to mark distinct regions of silent chromatin within the mammalian epigenome. Within eukaryotic nuclei, DNA associates with nuclear proteins to form chromatin. The most fundamental structural unit of chromatin, the nucleosome, is composed of ∼146 bp of DNA wrapped around an octamer of the core histone proteins H2A, H2B, H3, and H4 (1van Holde K.E. Chromatin.in: Rich A. Springer Series in Molecular Biology. Springer-Verlag New York Inc., New York1988Google Scholar). Although much has been elucidated about chromatin in the last decade, it remains unclear how distinct functional domains of chromatin are established and maintained within living cells. It is well known that chromatin function is modulated, at least in part, by enzymes that post-translationally modify specific amino acids on the histone proteins (2Wolffe A.P. Hayes J.J. Nucleic Acids Res. 1999; 27: 711-720Crossref PubMed Scopus (441) Google Scholar). Such post-translational modifications include acetylation, phosphorylation, ubiquitination, and methylation (3Peterson C.L. Laniel M.A. Curr. Biol. 2004; 14: R546-R551Abstract Full Text Full Text PDF PubMed Scopus (1003) Google Scholar). Increasing evidence indicates that specific covalent modifications, alone or in combination, directly participate in specific downstream nuclear processes including transcription, replication, and repair (4Jenuwein T. Allis C.D. Science. 2001; 293: 1074-1080Crossref PubMed Scopus (7816) Google Scholar). Thus, it is theorized that this “histone code” may serve to establish and maintain distinct functional domains that are epigenetically transmitted (5Strahl B.D. Allis C.D. Nature. 2000; 403: 41-45Crossref PubMed Scopus (6782) Google Scholar, 6Turner B.M. BioEssays. 2000; 22: 836-845Crossref PubMed Scopus (986) Google Scholar, 7Turner B.M. Cell. 2002; 111: 285-291Abstract Full Text Full Text PDF PubMed Scopus (941) Google Scholar). One histone modification that has received increased attention is the methylation of lysine 20 on histone H4 (H4 Lys-20). 2The abbreviations used are: H4 Lys-20, histone H4 lysine 20; H3 Lys-9, histone H3 lysine 9; H4 Lys-16, histone H4 lysine 16; H2B Lys-123, histone H2B lysine 123; HMT, histone methyltransferase; MEF, mouse embryonic fibroblast; FITC, fluorescein isothiocyanate; DAPI, 4′,6-diamidino-2-phenylindole; pol, polymerase. Although this methylated histone lysine residue was identified over 40 years ago, the biological significance of this modification has remained enigmatic (8Murray K. Biochemistry. 1964; 3: 10-15Crossref PubMed Scopus (346) Google Scholar). Investigations into H4 Lys-20 methylation were complicated by the fact that the epsilon amino group of lysine residues can be mono-, di-, or trimethylated in vivo (9Zhang K. Tang H. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 2003; 783: 173-179Crossref PubMed Scopus (36) Google Scholar). The recent discovery of the histone methyltransferase enzymes (HMTs) responsible for making the specific H4 Lys-20 methyl modifications have led to important insights into their potential biological functions (10Fang J. Feng Q. Ketel C.S. Wang H. Cao R. Xia L. Erdjument-Bromage H. Tempst P. Simon J.A. Zhang Y. Curr. Biol. 2002; 12: 1086-1099Abstract Full Text Full Text PDF PubMed Scopus (273) Google Scholar, 11Nishioka K. Rice J.C. Sarma K. Erdjument-Bromage H. Werner J. Wang Y. Chuikov S. Valenzuela P. Tempst P. Steward R. Lis J.T. Allis C.D. Reinberg D. Mol. Cell. 2002; 9: 1201-1213Abstract Full Text Full Text PDF PubMed Scopus (475) Google Scholar, 12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar). PR-Set7, also known as Set8, is responsible for the majority of monomethylated H4 Lys-20, whereas the Suv4-20 HMTs are responsible for the bulk of trimethylated H4 Lys-20 in flies and humans (12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar, 13Couture J.F. Collazo E. Brunzelle J.S. Trievel R.C. Genes Dev. 2005; 19: 1455-1465Crossref PubMed Scopus (194) Google Scholar, 14Xiao B. Jing C. Kelly G. Walker P.A. Muskett F.W. Frenkiel T.A. Martin S.R. Sarma K. Reinberg D. Gamblin S.J. Wilson J.R. Genes Dev. 2005; 19: 1444-1454Crossref PubMed Scopus (156) Google Scholar, 15Yin Y. Liu C. Tsai S.N. Zhou B. Ngai S.M. Zhu G. J. Biol. Chem. 2005; 280: 30025-30031Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Recent studies strongly suggest that H4 Lys-20 methylation and the HMTs that create these marks are involved in many important DNA-associated processes including transcriptional silencing, higher order chromatin structure, differentiation, genomic stability, and cell division (12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar, 16Biron V.L. McManus K.J. Hu N. Hendzel M.J. Underhill D.A. Dev. Biol. 2004; 276: 337-351Crossref PubMed Scopus (72) Google Scholar, 17Julien E. Herr W. Mol. Cell. 2004; 14: 713-725Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar, 18Karachentsev D. Sarma K. Reinberg D. Steward R. Genes Dev. 2005; 19: 431-435Crossref PubMed Scopus (148) Google Scholar, 19Martens J.H. O'Sullivan R.J. Braunschweig U. Opravil S. Radolf M. Steinlein P. Jenuwein T. EMBO J. 2005; 24: 800-812Crossref PubMed Scopus (527) Google Scholar, 20Rice J.C. Nishioka K. Sarma K. Steward R. Reinberg D. Allis C.D. Genes Dev. 2002; 16: 2225-2230Crossref PubMed Scopus (203) Google Scholar, 21Stadler F. Kolb G. Rubusch L. Baker S.P. Jones E.G. Akbarian S. J. Neurochem. 2005; 94: 324-336Crossref PubMed Scopus (79) Google Scholar). In addition, a recent finding indicates that H4 Lys-20 methylation and the H4 Lys-20 HMT homologue in fission yeast play a role in DNA double-strand break repair, although this has yet to be confirmed in higher eukaryotes (22Sanders S.L. Portoso M. Mata J. Bahler J. Allshire R.C. Kouzarides T. Cell. 2004; 119: 603-614Abstract Full Text Full Text PDF PubMed Scopus (462) Google Scholar). To further study the function(s) of the different methylated states of H4 Lys-20, we created a novel panel of H4 Lys-20 methyl-specific antibodies. Use of these antibodies in indirect immunofluorescence studies revealed that the mono-, di-, and trimethylated forms of H4 Lys-20 partitioned to distinct compartments of silent chromatin in the mammalian nucleus. Because we had of the methylated forms of histone H3 lysine 9 (H3 Lys-9) S. K. O'Sullivan R.J. L. A. Opravil S. M. Y. J.H. Jenuwein T. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar, J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google a direct comparison was between the different methylated states of H4 Lys-20 and H3 we that was a within the same silent nuclear compartments specifically for methylated states of H4 Lys-20 and H3 Consistent were on chromatin analysis revealed that monomethylated H4 Lys-20 and H3 Lys-9 were preferentially and selectively enriched on the same nucleosome core in vivo. Collectively, findings that a trans-tail histone code involving monomethylated H4 Lys-20 and H3 Lys-9 in higher eukaryotes and is to play an important role in the of a specific chromatin and of histone of and cell were by to in and with the H4 Lys-20 or antibodies in for at in were with a in for at to the of were by to for was with of for at to the cell cells. The used for these studies to residues of histone embryonic were and as J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). used were as H4 Lys-20 and H3 Lys-9 and was as J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). was a on a were were as with the modifications Mol. Biol. 2004; PubMed Scopus Google Scholar). were nuclear and by were in and to chromatin that was and in for 20 at were in and for at antibodies were in and to by an at were in to a with antibodies. was a on a and were with were were in to a of as by was to the and for 20 at The was with and were by One of were with of the H4 Lys-20 or of the H4 Lys-20 in and with were in or The was in by for was used to of the and of the was to and with the methyl-specific antibodies. of H4 Lys-20 the biological significance of the different states of H4 Lys-20 methylation, antibodies were amino acids of the histone H4 a mono-, di-, or trimethylated Lys-20 residue L. Opravil S. M. K. Jenuwein T. 2004; PubMed Scopus Google Scholar). analysis that specifically detected histone H4 as the antibodies to the histone H4 or cell To the H4 Lys-20 methyl of the were used in as J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). The that the H4 Lys-20 mono-, di-, and trimethylated were to the of the H4 Lys-20 mono-, di-, and confirmed that the antibodies are also specific in immunofluorescence and and of monomethylated H4 Lys-20 and H3 Lys-9 on the same core particle in vivo. were with the H4 Lys-20 analysis of of the and of the indicates that the are specifically enriched for the monomethylated form of H4 Lys-20. most by both the and the analysis with antibodies. analysis of the H4 Lys-20 indicates that are also selectively enriched for monomethylated H3 were with the H4 Lys-20 analysis of of the and of the indicates that the are specifically enriched for the trimethylated form of H4 Lys-20. analysis of the H4 Lys-20 indicates that is a for trimethylated H3 Lys-9 in although the mono- and dimethylated forms of H3 Lys-9 are also detected to a Consistent were in for methyl-specific One potential associated with antibodies is a in post-translational modifications the of the to To H4 acetylation, the known potential modification to H4 Lys-20, the of the antibodies to H4 Lys-20 methylation, were the yeast S. J. A. P. L. J. EMBO J. 1999; 18: PubMed Scopus Google Scholar, P.A. L. J. S.M. R. R. T. Allis C.D. F. S.L. Genes Dev. PubMed Scopus Google Scholar). Although significant in H4 were detected by the of H4 Lys-20 methyl antibodies were by in H4 antibodies specific to the mono-, di-, or trimethylated form of H4 Lys-20 were and be used to investigate the biological of of these histone modifications. of H4 Lys-20 to the nuclear of of the H4 Lys-20 methyl modifications, immunofluorescence were in the methyl-specific antibodies. in mono- and dimethylated H4 Lys-20 were the to be to specific as by their H4 Lys-20 to be enriched the nuclear was and was enriched within the of the chromosome and A. F. Lachner M. J. Jenuwein T. A. Biol. 2004; PubMed Scopus Google Scholar). In dimethylated H4 Lys-20 was the was in the and was enriched on the mono- and modifications were the pericentric trimethylated H4 Lys-20 was N. P. S. P. R. S. G. L. S. W. R. J. Sci. 2004; PubMed Scopus Google Scholar). To mono- and dimethylated H4 Lys-20 were within nuclear were as J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). in mono- and dimethylated H4 Lys-20 to be as by the of methylated states of H4 Lys-20 and H3 Lys-9 to the same silent nuclear for monomethylated H4 Lys-20 and mono- or dimethylated H3 Lys-9 H4 Lys-20 and H3 Lys-9 are preferentially enriched within the same silent nuclear compartments as by the of in the In monomethylated H4 Lys-20 is dimethylated H3 Lys-9 regions on the chromosome for dimethylated H4 Lys-20 and mono- or dimethylated H3 Lys-9 H4 Lys-20 and H3 Lys-9 to silent nuclear compartments in the although are also regions are exclusive. H4 Lys-20 to monomethylated H3 Lys-9 nuclear for trimethylated H4 Lys-20 and H3 Lys-9 modifications are enriched within pericentric heterochromatin. Although it was that trimethylated H4 Lys-20 was enriched within the for mono- and dimethylated H4 Lys-20 were of transcriptionally chromatin. To these modifications were associated with regions of the were with the methyl-specific antibodies and a In was the and was the with revealed that the majority of mono- and dimethylated H4 Lys-20 was transcriptionally as by the of in the that the majority of forms of H4 Lys-20 methylation are enriched within silent chromatin. Collectively, these findings that mono-, di-, and trimethylated H4 Lys-20 are to distinct transcriptionally nuclear of H4 Lys-20 and H3 Lys-9 within the nuclear of the methylated forms of H4 Lys-20 were to the of the methylated forms of H3 Lys-9 S. K. O'Sullivan R.J. L. A. Opravil S. M. Y. J.H. Jenuwein T. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar, J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). on this, we that methylated states of H4 Lys-20 and H3 Lys-9 were to the same silent nuclear To this were in of the methyl-specific antibodies Consistent with the bulk of both trimethylated H4 Lys-20 and trimethylated H3 Lys-9 was enriched within pericentric (12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar, N. P. S. P. R. S. G. L. S. W. R. J. Sci. 2004; PubMed Scopus Google Scholar). to the majority of monomethylated H4 Lys-20 was to the same nuclear compartments as monomethylated H3 Lys-9 Although the overlap between monomethylated H4 Lys-20 and dimethylated H3 Lys-9 was on the was with monomethylated H3 H4 Lys-20 to preferentially to dimethylated H3 Lys-9 compartments with monomethylated H3 Lys-9 Although dimethylated H4 Lys-20 and H3 Lys-9 to the same also to be many regions these modifications were exclusive. In that the majority of monomethylated H4 Lys-20 and H3 Lys-9 are enriched within the same transcriptionally silent nuclear of H4 Lys-20 and H3 Lys-9 within the the of these different methyl modifications at higher were on chromatin the methyl-specific antibodies to the findings in the nuclei, the monomethylated forms of H4 Lys-20 and H3 Lys-9 were preferentially to the same silent regions the chromatin The well of these histone modifications strongly that are enriched within specific genomic although these regions are It is important to that although monomethylated H4 Lys-20 with monomethylated H3 Lys-9, monomethylated H3 Lys-9 was also in silent regions the chromatin that were of monomethylated H4 Lys-20 In dimethylated H3 Lys-9 was the of the chromatin with the findings in nuclei, to be preferentially enriched in the same regions as dimethylated H3 Lys-9 Although dimethylated H4 Lys-20 also to to regions the chromatin that were enriched in monomethylated H3 Lys-9, of these regions revealed that dimethylated H4 Lys-20 was the monomethylated H3 Lys-9 regions were for trimethylated H4 Lys-20. Although we that this modification was to pericentric and be to on chromatin trimethylated H4 Lys-20 was enriched within specific regions the of the trimethylated H3 Lys-9 to these mono- and dimethylated H3 Lys-9 also to these although much Collectively, these the findings and suggest that methylated states of H4 Lys-20 and H3 Lys-9 mono-, di-, or are to the same genomic regions of silent chromatin. H4 Lys-20 and H3 Lys-9 to the in findings that methylated states of H4 Lys-20 and H3 Lys-9 be enriched within the same core the mono- and trimethylated To this, were with the mono- or H4 Lys-20 antibodies on the analysis of the was to the of the H4 Lys-20 specifically enriched for this whereas and trimethylated H4 Lys-20 were Similarly, the H4 Lys-20 enriched for this modification for the mono- or dimethylated H4 Lys-20 Although were with the H4 Lys-20 we were in specifically enriched for dimethylated H4 Lys-20. were on the the H3 Lys-9 methyl-specific antibodies. Consistent with the immunofluorescence monomethylated H3 Lys-9 was detected in monomethylated H4 and trimethylated H3 Lys-9 were detected within these to the chromatin trimethylated H3 Lys-9 was preferentially detected in the H4 Lys-20 however, mono- and dimethylated H3 Lys-9 were also to a Although the of these remains it findings that the monomethylated forms of H4 Lys-20 and H3 Lys-9 were specifically enriched within the same core a trans-tail histone code involving these marks is associated with distinct regions of silent chromatin. Although have been known to be methylated in the biological of this modification has remained J.C. Allis C.D. Curr. Biol. 2001; PubMed Scopus Google Scholar). In this we to further the of the biological role(s) of the mono-, di-, and trimethylated forms of H4 Lys-20, the methylated histone lysine residue (8Murray K. Biochemistry. 1964; 3: 10-15Crossref PubMed Scopus (346) Google Scholar). To this we created a novel panel of H4 Lys-20 methyl-specific antibodies with the methyl modifications on Lys-20, are by the of H4 These methyl-specific antibodies were used to that methylated form of H4 Lys-20 to distinct nuclear compartments that at least by indirect to be transcriptionally chromatin we had different HMTs are responsible for the specific of methylation of a specific histone residue in vivo J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). these findings strongly suggest that the are to distinct genomic by to create these histone in distinct transcriptionally chromatin recent report that monomethylated H4 Lys-20 was associated with transcriptionally chromatin as by with and H4 indirect immunofluorescence in mouse H. B. W. J. Biol. Chem. 2005; 280: Full Text Full Text PDF PubMed Scopus Google Scholar). analysis of the a that is of mouse T. K. M. Sci. U. S. A. 2001; PubMed Scopus Google a in monomethylated H4 Lys-20 at the and in mouse with cells. In to these are in with that monomethylated H4 Lys-20 is associated with transcriptionally silent chromatin in higher eukaryotes (10Fang J. Feng Q. Ketel C.S. Wang H. Cao R. Xia L. Erdjument-Bromage H. Tempst P. Simon J.A. Zhang Y. Curr. Biol. 2002; 12: 1086-1099Abstract Full Text Full Text PDF PubMed Scopus (273) Google Scholar, 11Nishioka K. Rice J.C. Sarma K. Erdjument-Bromage H. Werner J. Wang Y. Chuikov S. Valenzuela P. Tempst P. Steward R. Lis J.T. Allis C.D. Reinberg D. Mol. Cell. 2002; 9: 1201-1213Abstract Full Text Full Text PDF PubMed Scopus (475) Google Scholar, 18Karachentsev D. Sarma K. Reinberg D. Steward R. Genes Dev. 2005; 19: 431-435Crossref PubMed Scopus (148) Google Scholar, 19Martens J.H. O'Sullivan R.J. Braunschweig U. Opravil S. Radolf M. Steinlein P. Jenuwein T. EMBO J. 2005; 24: 800-812Crossref PubMed Scopus (527) Google Scholar, A. F. Lachner M. J. Jenuwein T. A. Biol. 2004; PubMed Scopus Google Scholar, A. M. D. Erdjument-Bromage H. Tempst P. Reinberg D. Mol. Cell. 2004; 16: Full Text Full Text PDF PubMed Scopus Google Scholar). Although the for this is it recent that specific histone modifications can also be associated with a DNA-templated at least in mouse cells. it was that trimethylated H3 Lys-9, has a of chromatin, was enriched within the regions of including in mouse of Mol. Cell. 2005; 19: Full Text Full Text PDF PubMed Scopus Google Scholar). although we that the majority of monomethylated H4 Lys-20 is associated with chromatin it may also serve an role in the of mouse associated with It is these are for of in different cell further are to Consistent with we trimethylated H4 Lys-20 enriched within the and of pericentric J.H. O'Sullivan R.J. Braunschweig U. Opravil S. Radolf M. Steinlein P. Jenuwein T. EMBO J. 2005; 24: 800-812Crossref PubMed Scopus (527) Google Scholar). These findings that this modification may specifically mark regions of regions that are to be W. 1999; PubMed Scopus Google Scholar). We that the bulk of monomethylated H4 Lys-20 was enriched within silent regions of the chromosome and was also enriched within the chromosome and These findings that this modification may specifically mark regions of chromatin that is silent has the to this is dimethylated H4 Lys-20 into the types of modification is of mono- and trimethylated H4 Lys-20, and and on this, it is that dimethylated H4 Lys-20 may define an of that has yet been The discovery of the HMT responsible for H4 Lys-20 insights into this Because we had nuclear of the different methylated states of H3 Lys-9 J.C. B. J. Y. Allis C.D. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google we that both modifications together within these silent by findings that the methylated states of H4 Lys-20 and H3 Lys-9 to to the same silent compartments in the and within the same genomic regions on chromatin at the revealed that monomethylated H4 Lys-20 and H3 Lys-9 were preferentially and selectively enriched on the same nucleosome core particle in vivo. Collectively, these findings that a trans-tail histone code in the mammalian monomethylated H4 Lys-20 and H3 Lys-9 on the same nucleosome to mark a distinct chromatin To are of trans-tail histone involving H2B and H3 methylation J. J. M.A. A. K. M. A. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Allis C.D. Nature. 2002; PubMed Scopus Google or H3 methylation T. J.A. J. Allis C.D. B.D. Nature. 2002; PubMed Scopus Google Scholar, Zhang Y. K. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google in yeast and of H4 Lys-20 and H3 Lys-9 in (12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar). We a histone code involving monomethylated H4 Lys-20 and H3 Lys-9 and for the that the modifications on the same nucleosome in vivo. recent study of a H4 Lys-20 and H3 Lys-9 trans-tail histone code J.H. O'Sullivan R.J. Braunschweig U. Opravil S. Radolf M. Steinlein P. Jenuwein T. EMBO J. 2005; 24: 800-812Crossref PubMed Scopus (527) Google Scholar). of in mouse embryonic revealed specific of for specific methyl modifications within different The of both monomethylated H4 Lys-20 and monomethylated H3 Lys-9 was in whereas the and trimethylated forms of H4 Lys-20 or H3 Lys-9 were both modifications were at and DNA and to this of and exclusion to be for Although trimethylated H4 Lys-20 and H3 Lys-9 were both strongly enriched within their of within trimethylated H3 Lys-9 was enriched within DNA trimethylated H4 Lys-20 was and trimethylated H4 Lys-20 was enriched within and trimethylated H3 Lys-9 was is with findings that was a of trimethylated H4 Lys-20 and H3 Lys-9 on chromatin and that mono- and dimethylated H3 Lys-9 also be to a these recent evidence indicates that is a H4 Lys-20 and H3 Lys-9 trans-tail histone code specifically at pericentric (12Schotta G. Lachner M. Sarma K. Ebert A. Sengupta R. Reuter G. Reinberg D. Jenuwein T. Genes Dev. 2004; 18: 1251-1262Crossref PubMed Scopus (879) Google Scholar). In this the of the HMTs in the of trimethylated H3 Lys-9 also in the of trimethylated H4 Lys-20 within pericentric These findings that the of H4 Lys-20 is the of H3 Similarly, in the methylation of both H3 and are the of H2B by J. J. M.A. A. K. M. A. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Allis C.D. Nature. 2002; PubMed Scopus Google Scholar, T. J.A. J. Allis C.D. B.D. Nature. 2002; PubMed Scopus Google Scholar, Zhang Y. K. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). in trans-tail histone is a of modification We on the established for the of H3 Lys-9 of H4 Lys-20, although this has yet to be Although findings define a novel trans-tail histone code associated with a distinct of chromatin, the biological function(s) of this are The of the as well as the genomic of this be to the of the monomethylated H4 Lys-20 and H3 Lys-9 trans-tail histone We for the and histone and for of the chromatin and with and the and and of the Rice for and with