Identification of Lysine 37 of Histone H2B as a Novel Site of Methylation

Gardner, Kathryn E.; Zhou, Li; Parra, Michael A.; Chen, Xian; Strahl, Brian D.

doi:10.1371/journal.pone.0016244

Cited by 29 publications

(30 citation statements)

References 108 publications

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“…The development of more powerful methods to detect histone posttranslational modifications has identified residues within or adjacent to the HBR domain that are modified. Methylation and acetylation of lysine 37 have been detected (62,63). Modification of K37 could affect the ability of FACT to engage the dimer.…”

Section: Discussionmentioning

confidence: 99%

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A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

Zheng

Crickard

Srikanth

et al. 2014

Molecular and Cellular Biology

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Histone N-terminal tails play crucial roles in chromatin-related processes. The tails of histones H3 and H4 are highly conserved and well characterized, but much less is known about the functions of the tails of histones H2A and H2B and their sequences are more divergent among eukaryotes. Here we characterized the function of the only highly conserved region in the H2B tail, the H2B repression (HBR) domain. Once thought to play a role only in repression, it also has an uncharacterized function in gene activation and DNA damage responses. We report that deletion of the HBR domain impairs the eviction of nucleosomes at the promoters and open reading frames of genes. A closer examination of the HBR domain mutants revealed that they displayed phenotypes similar to those of histone chaperone complex FACT mutants, including an increase in intragenic transcription and the accumulation of free histones in cells. Biochemical characterization of recombinant nucleosomes indicates that deletion of the HBR domain impairs FACT-dependent removal of H2A-H2B from nucleosomes, suggesting that the HBR domain plays an important role in allowing FACT to disrupt dimer-DNA interactions. We have uncovered a previously unappreciated role for the HBR domain in regulating chromatin structure and have provided insight into how FACT acts on nucleosomes.T he genomes of eukaryotes are packaged into chromatin, which is composed of DNA and the four core histones H2A, H2B, H3, and H4 (1, 2). Each histone contains an N-terminal tail that can be decorated with multiple posttranslational modifications. The modification of residues in the tails controls nuclear functions such as gene expression, mitosis, meiosis, mRNA processing, gene silencing, and DNA repair (2-4). The N-terminal tails of histones H3 and H4 are exceptionally well conserved across all eukaryotes, including the sites of posttranslational modifications. The importance of these tails in regulating chromatin transactions has been interrogated by many studies using the genetically tractable yeast model system. In contrast, the amino acid sequence of the H2A and H2B N-terminal tails are relatively divergent between yeasts and metazoans; thus, much less is known about their functions than about those of H3 and H4.While most of the yeast H2B (yH2B) tail shows minimal sequence similarity to its metazoan counterparts, a short basic region (residues 30 to 37) known as the H2B repression (HBR) domain is highly conserved among all eukaryotes (5, 6). The HBR is located adjacent to the ␣-helical structured region in the H2B tail and passes between the gyres of DNA within the structure of the nucleosome. First it was thought to play a role only in the silencing of telomere-proximal genes, but recent analysis of a mutant containing a deletion of the HBR domain (⌬HBR) revealed that it is important also for DNA damage repair and the activation and repression of genes (7,8). Since the HBR domain residues make contact with DNA, the mutant phenotypes were attributed to weakened histone-DNA interactions....

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Section: Discussionmentioning

confidence: 99%

“…Modification of K37 could affect the ability of FACT to engage the dimer. The effects would have to be subtle, however, because K37 mutants (A or R substitutions) have no phenotypes in common with FACT or ⌬HBR mutants (62). It is important to note that residues flanking the HBR domain also may be important.…”

Section: Discussionmentioning

confidence: 99%

A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

Zheng

Crickard

Srikanth

et al. 2014

Molecular and Cellular Biology

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“…Briefly, 63 deletion strains (Table 3) were mated to the temperaturesensitive cdc6-1 strain (JCY332), and haploids carrying both mutations were isolated by growth on selective media. All of the deletion strains originated from the Yeast Knock Out library (Open Biosystems) except strains lacking SET1 or DOT1; the set1D strains were created de novo while the dot1D strain was previously published (Gardner et al 2011). Additionally, SET1 and BRE1 deletions were recreated de novo in the cdc6-1 mutant in the BY4741 background (yLF058).…”

Section: Synthetic Genetic Array Screenmentioning

confidence: 99%

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

et al. 2012

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DNA replication is a highly regulated process that is initiated from replication origins, but the elements of chromatin structure that contribute to origin activity have not been fully elucidated. To identify histone post-translational modifications important for DNA replication, we initiated a genetic screen to identify interactions between genes encoding chromatin-modifying enzymes and those encoding proteins required for origin function in the budding yeast Saccharomyces cerevisiae. We found that enzymes required for histone H3K4 methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase Bre1, are required for robust growth of several hypomorphic replication mutants, including cdc6-1. Consistent with a role for these enzymes in DNA replication, we found that both Set1 and Bre1 are required for efficient minichromosome maintenance. These phenotypes are recapitulated in yeast strains bearing mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains lacking specific COMPASS complex members or containing H2B mutations that differentially affect H3K4 methylation states, we determined that these replication defects were due to loss of H3K4 di-methylation. Furthermore, histone H3K4 di-methylation is enriched at chromosomal origins. These data suggest that H3K4 di-methylation is necessary and sufficient for normal origin function. We propose that histone H3K4 di-methylation functions in concert with other histone posttranslational modifications to support robust genome duplication. DNA replication initiates at discrete genomic loci termed "origins of replication." Each eukaryotic chromosome is replicated from many individual origins to ensure complete and precise genome duplication during each cell division cycle. Individual origins vary both in the likelihood that they will initiate replication, or "fire," in any given S phase and in the firing time within the S phase (Weinreich et al. 2004). Highly efficient origins fire in most cell cycles, whereas inefficient origins fire in only some cycles and are usually passively replicated by forks emanating from neighboring efficient origins. Although highly efficient origins that support initiation in most cell cycles have been identified in many genomes, the chromosomal determinants of origin location and function are still incompletely understood. Strikingly, while DNA sequence elements can be necessary, it is clear that sequence alone is insufficient to fully specify eukaryotic origin location and activity (Méchali 2010).Like all DNA-templated processes, replication occurs on chromatin. Recent progress in the field has demonstrated that the chromatin structure surrounding origins plays an essential role in controlling origin activity. For example, the positioning of nucleosomes near origins can either stimulate or inhibit origin function (Simpson 1990;Crampton et al. 2008;Berbenetz et al. 2010;Eaton et al. 2010). The major protein compon...

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“…In eukaryotes, histone lysine methylation occurs on histone H3 at lysines 4, 9, 14, 27, 36, and 79 and on histone H4 at lysines 20 and 59 (Strahl and Allis, 2000;Berger, 2002;Zhang et al, 2002;Zhang et al, 2003). A recent study provide evidences that methylation can also occurs on Lysine 37 of histone H2B in vivo (Gardner et al, 2011). In A. thaliana, the best known histone lysine methylation occurs at Lys4 (K4), Lys9 (K9), Lys27 (K27), and Lys36 (K36) of histone H3 while methylation on lysine 20 of H4 has only been observed with immunostaining.…”

Section: Histone Lysine Methylationsmentioning

confidence: 99%

Post-Translational Modifications of Nuclear Proteins in the Response of Plant Cells to Abiotic Stresses

Dahan¹,

Koen²,

Dutartre³

et al. 2011

Abiotic Stress Response in Plants - Physiological, Biochemical and Genetic Perspectives

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Identification of Lysine 37 of Histone H2B as a Novel Site of Methylation

Cited by 29 publications

References 108 publications

A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

Post-Translational Modifications of Nuclear Proteins in the Response of Plant Cells to Abiotic Stresses

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