A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

Lei, Bingkun; Capella, Matías; Montgomery, Sean A.; Borg, Michael; Osakabe, Akihisa; Goiser, Malgorzata; Muhammad, Abubakar Sadiq; Braun, Sigurd; Berger, Frédéric

doi:10.1016/j.cub.2020.09.080

Cited by 19 publications

(16 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fission yeast possesses a relatively reduced repertoire of histone H2A variants, consisting of two H2A.X variants (SpH2A.α and SpH2A.β) and H2A.Z [54,55]. We modified both genes encoding SpH2A by inserting the C-terminal tail of the Arabidopsis H2A.W.6 to the C-terminus of SpH2A.α and SpH2A.β that contains an SQ motif, and obtained the chimeric histone SpH2A.W At that possesses the motifs present in H2A.W.7 [25] (Fig 5A, S5B Fig) Fig 5D). This suggested that either extension of the Cterminal tail or modification of the KSPK motif interfered with the DDR normally mediated by phosphorylation of the SQ motif.…”

Section: Cross Talk Between Phosphorylation At the Kspk Is Mediated Bmentioning

confidence: 99%

“…Gene replacement and tagging were performed by homologous recombination using a plasmid-based method [81]. The primers used are listed in S1 Table. In brief, pCloneNat1 and pCloneHyg1 were used to fuse the H2A.W.6 (At) C-terminal 21 amino acids to the endogenous C-terminus of SpH2A.α and SpH2A.β by using the natMX4 or hphMX4 cassette, respectively [25]. All constructed strains in this study were verified by PCR analysis and sequencing.…”

Section: Schizosaccharomyces Pombe Strains and Mediamentioning

confidence: 99%

“…The main feature defining H2A.W variants is the C-terminal KSPK motif [21,23]. Due to the expected location of the H2A.W C-terminus at the nucleosome dyad (entry/exit site of the DNA into the nucleosome), the KSPK motif is placed in a functionally significant area [24] where it interacts with the linker DNA [25]. This motif is a member of the S/T-P-X-K/R motifs (where X represents any amino acid) present in macroH2A in metazoans and linker histones H1 among other proteins [26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Schmuecker

Lei

Lorković

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Histone variants are distinguished by specific substitutions and motifs that might be subject to post-translational modifications (PTMs). Compared with the high conservation of H3 variants, the N- and C-terminal tails of H2A variants are more divergent and are potential substrates for a more complex array of PTMs, which have remained largely unexplored. We used mass spectrometry to inventory the PTMs of the two heterochromatin-enriched variants H2A.W.6 and H2A.W.7 of Arabidopsis, which harbor the C-terminal motif KSPK. This motif is also found in macroH2A variants in animals and confers specific properties to the nucleosome. We showed that H2A.W.6 is phosphorylated by the cell cycle-dependent kinase CDKA specifically at KSPK. In contrast, this modification is absent on H2A.W.7, which also harbors the SQ motif associated with the variant H2A.X. Phosphorylation of the SQ motif is critical for the DNA damage response but is suppressed in H2A.W.7 by phosphorylation of KSPK. To identify factors involved in this suppression mechanism, we performed a synthetic screen in fission yeast expressing a mimic of the Arabidopsis H2A.W.7. Among those factors was the BRCT-domain protein Mdb1. We showed that phosphorylation of KSPK prevents binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and as a result hampers response to DNA damage. Hence, cross-talks between motif-specific PTMs interfere with the vital functions of H2A variants. Such interference could be responsible for the mutual exclusion of specific motifs between distinct H2A variants. We conclude that sequence innovations in H2A variants have potentiated the acquisition of many specific PTMs with still unknown functions. These add a layer of complexity to the nucleosome properties and their impact in chromatin regulation.

show abstract

Section: Cross Talk Between Phosphorylation At the Kspk Is Mediated Bmentioning

confidence: 99%

Section: Schizosaccharomyces Pombe Strains and Mediamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Schmuecker

Lei

Lorković

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…H2A.W.12 is expressed only during the late phase of reproductive development and is less abundant than the two other variants [20]. H2A.W confers distinct properties to the nucleosome through differences in its primary amino acid sequence in the L1 loop, the docking domain, and the KSPK motif in the extended C-terminal tail [22,23]. Due to the expected location of the H2A.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the expected location of the H2A. W C-terminus at the nucleosome dyad (entry/exit site of the DNA into the nucleosome), the KSPK motif is placed in a functionally significant area [24] where it interacts with the linker DNA [23].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between H2A variant-specific modifications impacts vital cell functions

et al. 2021

Self Cite

View full text Add to dashboard Cite

Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.

show abstract

Diversification of chromatin organization in eukaryotes

Jamge

Berger

2022

Current Opinion in Cell Biology

View full text Add to dashboard Cite

A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

Abstract: Highlights d Selection of the motif KSPK marks evolution of H2A.W in vascular plants d Synthetic addition of the KSPK motif to yeast H2A affects only heterochromatin d Histone variants can be selected prior to their segregation to chromatin domains

Cited by 19 publications

References 67 publications

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Diversification of chromatin organization in eukaryotes

Contact Info

Product

Resources

About