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Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.

Horikoshi N, Sato K, Shimada K, Arimura Y, Osakabe A, Tachiwana H, Hayashi-Takanaka Y, Iwasaki W, Kagawa W, Harata M, Kimura H, Kurumizaka H - Acta Crystallogr. D Biol. Crystallogr. (2013)

Bottom Line: The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical.It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2.These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

ABSTRACT
The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms, H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct functions in cell growth and gene expression. However, no structural differences between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined. The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical. This structural polymorphism may have been induced by a substitution that evolutionally occurred at the position of amino acid 38 and by the flexible nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational analysis revealed that the amino-acid difference at position 38 is at least partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.

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The L1 loops of H2A.Z.1 and H2A.Z.2 are flexible in nucleosomes. (a–c) The B factors for each Cα atom of H2A.Z.1 (a), H2A.Z.2 (b) and H2A (c) in the nucleosomes are plotted. The secondary structures of H2A.Z.1, H2A.Z.2 and H2A in the nucleosomes are shown at the top of each panel. (d) Close-up views of the L1 loop regions of H2A.Z.1 (left panel), H2A.Z.2 (centre panel) and H2A (right panel). The 2mFo − DFc maps of the L1 loop regions of H2A.Z.1, H2A.Z.2 and H2A were calculated and contoured at the 1.5σ level. (e) Close-up views of the α2 region of H2A.Z.1 (left panel) and H2A.Z.2 (right panel). The 2mFo − DFc maps of the α2 regions of H2A.Z.1 and H2A.Z.2 are presented (1.5σ level).
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fig3: The L1 loops of H2A.Z.1 and H2A.Z.2 are flexible in nucleosomes. (a–c) The B factors for each Cα atom of H2A.Z.1 (a), H2A.Z.2 (b) and H2A (c) in the nucleosomes are plotted. The secondary structures of H2A.Z.1, H2A.Z.2 and H2A in the nucleosomes are shown at the top of each panel. (d) Close-up views of the L1 loop regions of H2A.Z.1 (left panel), H2A.Z.2 (centre panel) and H2A (right panel). The 2mFo − DFc maps of the L1 loop regions of H2A.Z.1, H2A.Z.2 and H2A were calculated and contoured at the 1.5σ level. (e) Close-up views of the α2 region of H2A.Z.1 (left panel) and H2A.Z.2 (right panel). The 2mFo − DFc maps of the α2 regions of H2A.Z.1 and H2A.Z.2 are presented (1.5σ level).

Mentions: The structural differences between the H2A.Z.1 and H2A.Z.2 L1 loop regions may also reflect their flexible nature. Consistent with this idea, the B factors of the L1 loop regions of H2A.Z.1 and H2A.Z.2 are quite high compared with the surrounding region (Figs. 3 ▶a and 3 ▶b), unlike the L1 loop region of canonical H2A (Fig. 3 ▶c). The electron densities of the side-chain moieties of the L1 loops are ambiguous in both H2A.Z.1 and H2A.Z.2 (Fig. 3 ▶d, left and centre panels), although they are visible in the other H2A.Z.1 and H2A.Z.2 regions (Fig. 3 ▶e) and the H2A L1 loop (Fig. 3 ▶d, right panel), also suggesting high flexibility. These results indicated that the H2A.Z.1 and H2A.Z.2 L1 loop regions may be more flexible than the corresponding region of the canonical H2A.


Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.

Horikoshi N, Sato K, Shimada K, Arimura Y, Osakabe A, Tachiwana H, Hayashi-Takanaka Y, Iwasaki W, Kagawa W, Harata M, Kimura H, Kurumizaka H - Acta Crystallogr. D Biol. Crystallogr. (2013)

The L1 loops of H2A.Z.1 and H2A.Z.2 are flexible in nucleosomes. (a–c) The B factors for each Cα atom of H2A.Z.1 (a), H2A.Z.2 (b) and H2A (c) in the nucleosomes are plotted. The secondary structures of H2A.Z.1, H2A.Z.2 and H2A in the nucleosomes are shown at the top of each panel. (d) Close-up views of the L1 loop regions of H2A.Z.1 (left panel), H2A.Z.2 (centre panel) and H2A (right panel). The 2mFo − DFc maps of the L1 loop regions of H2A.Z.1, H2A.Z.2 and H2A were calculated and contoured at the 1.5σ level. (e) Close-up views of the α2 region of H2A.Z.1 (left panel) and H2A.Z.2 (right panel). The 2mFo − DFc maps of the α2 regions of H2A.Z.1 and H2A.Z.2 are presented (1.5σ level).
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fig3: The L1 loops of H2A.Z.1 and H2A.Z.2 are flexible in nucleosomes. (a–c) The B factors for each Cα atom of H2A.Z.1 (a), H2A.Z.2 (b) and H2A (c) in the nucleosomes are plotted. The secondary structures of H2A.Z.1, H2A.Z.2 and H2A in the nucleosomes are shown at the top of each panel. (d) Close-up views of the L1 loop regions of H2A.Z.1 (left panel), H2A.Z.2 (centre panel) and H2A (right panel). The 2mFo − DFc maps of the L1 loop regions of H2A.Z.1, H2A.Z.2 and H2A were calculated and contoured at the 1.5σ level. (e) Close-up views of the α2 region of H2A.Z.1 (left panel) and H2A.Z.2 (right panel). The 2mFo − DFc maps of the α2 regions of H2A.Z.1 and H2A.Z.2 are presented (1.5σ level).
Mentions: The structural differences between the H2A.Z.1 and H2A.Z.2 L1 loop regions may also reflect their flexible nature. Consistent with this idea, the B factors of the L1 loop regions of H2A.Z.1 and H2A.Z.2 are quite high compared with the surrounding region (Figs. 3 ▶a and 3 ▶b), unlike the L1 loop region of canonical H2A (Fig. 3 ▶c). The electron densities of the side-chain moieties of the L1 loops are ambiguous in both H2A.Z.1 and H2A.Z.2 (Fig. 3 ▶d, left and centre panels), although they are visible in the other H2A.Z.1 and H2A.Z.2 regions (Fig. 3 ▶e) and the H2A L1 loop (Fig. 3 ▶d, right panel), also suggesting high flexibility. These results indicated that the H2A.Z.1 and H2A.Z.2 L1 loop regions may be more flexible than the corresponding region of the canonical H2A.

Bottom Line: The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical.It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2.These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

ABSTRACT
The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms, H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct functions in cell growth and gene expression. However, no structural differences between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined. The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical. This structural polymorphism may have been induced by a substitution that evolutionally occurred at the position of amino acid 38 and by the flexible nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational analysis revealed that the amino-acid difference at position 38 is at least partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.

Show MeSH
Related in: MedlinePlus