Steps Toward Understanding the Inheritance of Repressive Methyl-Lysine Marks in Histones

Reinberg, Danny; Chuikov, Sergei; Farnham, Peggy J.; Karachentsev, Dmitry; Kirmizis, Antonis; Kuzmichev, Andrei; Margueron, Raphaël; Nishioka, Kusuki; Preissner, Tanja S.; Sarma, Kavitha; Abate‐Shen, Cory; Steward, Ruth; Vaquero, Alejandro

doi:10.1101/sqb.2004.69.171

Cited by 14 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in contrast to the methylation of H3, methylation of H4 has not been so clearly associated with transcriptional regulation (30,41,60). The mapping of H4 species methylated at K20 gave somewhat confusing results.…”

Section: Discussionmentioning

confidence: 99%

Monomethylation of Lysine 20 on Histone H4 Facilitates Chromatin Maturation

Scharf

Meier

Seitz

et al. 2009

Molecular and Cellular Biology

View full text Add to dashboard Cite

Histone modifications play an important role in shaping chromatin structure. Here, we describe the use of an in vitro chromatin assembly system from Drosophila embryo extracts to investigate the dynamic changes of histone modifications subsequent to histone deposition. In accordance with what has been observed in vivo, we find a deacetylation of the initially diacetylated isoform of histone H4, which is dependent on chromatin assembly. Immediately after deposition of the histones onto DNA, H4 is monomethylated at K20, which is required for an efficient deacetylation of the H4 molecule. H4K20 methylation-dependent dl(3)MBT association with chromatin and the identification of a dl(3)MBT-dRPD3 complex suggest that a deacetylase is specifically recruited to the monomethylated substrate through interaction with dl(3)MBT. Our data demonstrate that histone modifications are added and removed during chromatin assembly in a highly regulated manner.All DNA in a eukaryotic cell is assembled into chromatin to fit it into the restricted nuclear space and to organize the genome (29, 56). As the DNA content of a cell doubles during S-phase of the cell cycle, the cell has to provide sufficient histone molecules to package the newly replicated DNA into chromatin. This is achieved mainly by a coupling of histone and DNA synthesis (37). The progression of the DNA replication machinery disrupts the nucleosome in front of the replication fork, which is then reassembled onto the newly synthesized DNA strands in a random manner (15,20). The remaining gaps are subsequently filled up with newly translated histone molecules, leading to a mosaic pattern of new and old histone octamers (2, 21). This process is assisted by the action of nuclear chaperones, which bind to the histones before deposition (14, 34). The newly deposited histones are more loosely associated with the DNA than the bulk histones and mature slowly into a more stable chromatin structure. Assembly is achieved via an ordered deposition of H3 and H4, followed by the binding of H2A/H2B dimers and finally the interaction of the linker histone H1 with the chromatin fiber (19)(20)(21)(22)49).Posttranslational modifications of histone molecules are generally considered to play an important role during the establishment and maintenance of chromatin structures. The combination of histone modifications has been proposed to constitute a "histone code" (23, 55), which is involved in the maintenance of epigenetic information. However, it is unclear how histone modifications are replicated during cellular division and DNA repair when newly translated histones are deposited onto the DNA.Modification marks can be stably maintained through multiple mitotic divisions (3,23,30,55). However, for most histone modifications, the molecular mechanisms that regulate this maintenance have so far remained elusive. A key aspect of this maintenance or reestablishment of modification patterns is the precise copying of histone modification patterns from the parental histone to the newly synthesized on...

show abstract

Section: Discussionmentioning

confidence: 99%

Monomethylation of Lysine 20 on Histone H4 Facilitates Chromatin Maturation

Scharf

Meier

Seitz

et al. 2009

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Histone lysine methylation can be presented as mono-, di-, or trimethyl states, where each distinct methyl state confers different biological read-outs (Santos-Rosa et al 2002;Lachner et al 2004). Histone lysine trimethyl states, particularly for the repressive functions, appear relatively robust, since they are stably propagated during several cell divisions Reinberg et al 2004;Schotta et al 2004) and resist reprogramming in early mammalian embryos (Santos et al 2003).Until recently, no enzymatic mechanism had been described that would directly remove histone lysine methylation, although amine oxidation or radical attack by hydroxylation could destabilize the amino-methyl bond Bannister and Kouzarides 2005;Trewick et al 2005). Indeed, a lysine-specific demethylase 1 (LSD1) has been shown to demethylate H3K4me2 (an active mark) (Shi et al 2004) and, when associated with a different protein complex, also appears to convert H3K9me2 (a repressive mark) (Metzger et al 2005).…”

mentioning

confidence: 99%

“…These data reveal that certain members of the jmjC class of hydroxylases can work in a pathway that actively antagonizes a histone lysine trimethyl state. Histone lysine methylation is a central epigenetic modification with both activating and repressive roles in eukaryotic chromatin (Kouzarides 2002;Fischle et al 2003;Lachner et al 2004;Reinberg et al 2004). There are five lysine residues in the histone N termini that are prominently methylated, with H3K4 and H3K36 methylation primarily transducing activating functions, whereas H3K9, H3K27, and H4K20 methylation is mainly associated with repressed chromatin.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells

Fodor¹,

Kubicek²,

Yonezawa³

et al. 2006

Genes Dev.

332

301

View full text Add to dashboard Cite

Histone lysine trimethyl states represent some of the most robust epigenetic modifications in eukaryotic chromatin. Using a candidate approach, we identified the subgroup of murine Jmjd2 proteins to antagonize H3K9me3 at pericentric heterochromatin. H3K27me3 and H4K20me3 marks are not impaired in inducible Jmjd2b-GFP cell lines, but Jmjd2b also reduces H3K36 methylation. Since recombinant Jmjd2b appears as a very poor enzyme, we applied metabolic labeling with heavy methyl groups to demonstrate Jmjd2b-mediated removal of chromosomal H3K9me3 as an active process that occurs well before replication of chromatin. These data reveal that certain members of the jmjC class of hydroxylases can work in a pathway that actively antagonizes a histone lysine trimethyl state. Histone lysine methylation is a central epigenetic modification with both activating and repressive roles in eukaryotic chromatin (Kouzarides 2002;Fischle et al. 2003;Lachner et al. 2004;Reinberg et al. 2004). There are five lysine residues in the histone N termini that are prominently methylated, with H3K4 and H3K36 methylation primarily transducing activating functions, whereas H3K9, H3K27, and H4K20 methylation is mainly associated with repressed chromatin. Histone lysine methylation can be presented as mono-, di-, or trimethyl states, where each distinct methyl state confers different biological read-outs (Santos-Rosa et al. 2002;Lachner et al. 2004). Histone lysine trimethyl states, particularly for the repressive functions, appear relatively robust, since they are stably propagated during several cell divisions Reinberg et al. 2004;Schotta et al. 2004) and resist reprogramming in early mammalian embryos (Santos et al. 2003).Until recently, no enzymatic mechanism had been described that would directly remove histone lysine methylation, although amine oxidation or radical attack by hydroxylation could destabilize the amino-methyl bond Bannister and Kouzarides 2005;Trewick et al. 2005). Indeed, a lysine-specific demethylase 1 (LSD1) has been shown to demethylate H3K4me2 (an active mark) (Shi et al. 2004) and, when associated with a different protein complex, also appears to convert H3K9me2 (a repressive mark) (Metzger et al. 2005). Based on the reaction mechanism, LSD1 cannot act on a lysine trimethyl state, and more potent mechanisms, involving attack by oxygen radicals via hydroxylases/dioxygenases, have been postulated (Clissold and Ponting 2001;Trewick et al. 2005). This could be inferred from the activities of the Escherichia coli AlkB enzyme to counteract alkylating damage of DNA or from other protein hydroxylases, such as the jmjC (jumonji) domain containing protein Factor Inhibiting Hypoxia (FIH) (Lando et al. 2002). In Schizosaccharomyces pombe, there is one silencing modifier, Epe1, which also carries a jmjC domain, and this factor antagonizes repressive H3K9me2 at centromeric regions (Ayoub et al. 2003). In addition, there are several jmjC proteins that have been shown to be important transcriptional/chromatin regulators (Takeuchi et al. 19...

show abstract

“…Histone lysine trimethyl states, particularly those with repressive functions, appear relatively robust because they are stably propagated during several cell divisions (Lachner et al, 2004). Among the histone modifications, histone H3 lysine (K) methylation is a central epigenetic modification with both activating and repressive roles in eukaryotic chromatin (Reinberg et al, 2004). JmjC domain proteins demethylate histone lysine and arginine residues in an oxidative reaction that requires Fe (II) and α-ketoglutarate as cofactors.…”

Section: Epigenetic Significance In Nsc-inflammationmentioning

confidence: 99%