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Asf1 is the budding-yeast ASF1-family histone chaperone that binds histones
H3-H4 and participates in nucleosome assembly across DNA-templated processes,
including DNA replication and transcription-associated chromatin remodeling.
"In yeast, **Asf1 is a histone chaperone that binds histones H3–H4** and participates in nucleosome assembly in multiple DNA-templated processes, including DNA replication and transcription-associated chromatin remodeling."
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Asf1 binds H3-H4 dimers and shields the surface required to form a stable
(H3-H4)2 tetramer, controlling histone oligomerization state during handling
and handoff.
"**Core chaperone activity:** Asf1 binds **H3–H4 dimers** and shields the surface needed to form a stable (H3–H4)2 tetramer, thereby controlling histone oligomerization state during handling/transport and handoff."
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The conserved N-terminal region of Asf1 forms a globular core with acidic
patches that contact the C-terminal region of histone H3 and can also bind H4,
consistent with its role as an H3-H4 chaperone.
"The conserved N-terminal region forms a globular core with acidic patches that contact histone H3 (C-terminal region) and can also bind H4, consistent with Asf1’s role as an H3–H4 chaperone."
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In the canonical handoff cascade, Asf1 binds newly synthesized H3-H4 (described
as occurring in the cytoplasm), promotes nuclear import/availability, and
presents H3-H4 to Rtt109 for acetylation of H3K56.
"- **Asf1 binds newly synthesized H3–H4** (described as occurring in the cytoplasm in one mechanistic account), promotes nuclear import/availability, and **presents H3–H4 to Rtt109** for acetylation of **H3K56**."
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Asf1 is solely required for H3K56 acetylation in yeast cells, and loss of Asf1
markedly decreases Rtt109 activity and H3K56ac.
"Asf1 is described as **solely required for H3K56ac in yeast cells** in the Dannah thesis excerpts, and loss of Asf1 markedly decreases Rtt109 activity and H3K56ac."
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After H3K56 acetylation, H3-H4 dimers are transferred to downstream deposition
chaperones, including CAF-1 (which accepts H3-H4 via a direct Cac2-Asf1
interaction) and Rtt106.
"**CAF-1 physical link:** CAF-1 is reported to accept H3–H4 via direct interaction between CAF-1 subunit **Cac2** and Asf1 in one mechanistic account."
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Asf1 works together with the HIR complex and Rtt106 to mediate
replication-independent H3-H4 deposition and to maintain promoter fidelity,
connecting it to transcriptional regulation through chromatin assembly and
disassembly dynamics.
"A 2024 *Molecular Cell* study supports that **Asf1 works together with the HIR complex (and with Rtt106) to mediate replication-independent H3–H4 deposition and maintain promoter fidelity**, connecting Asf1 to transcriptional regulation through chromatin assembly/disassembly dynamics."
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Asf1 participates in histone gene transcriptional activation in S phase and
transcriptional repression outside S phase, in combination with Hir1.
"In yeast-focused statements summarized in a 2024 preprint, Asf1 is described as participating in **histone gene transcriptional activation in S phase** and **transcriptional repression outside S phase** in combination with **Hir1** (a yeast counterpart of metazoan HIRA pathway components)."
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Asf1 contains a functional classical nuclear localization signal (cNLS) in its
highly acidic C-terminal tail; removal of this motif makes Asf1 fully
cytoplasmic, indicating the motif is required for nuclear localization.
"Asf1 contains a **functional classical nuclear localization signal (cNLS) in its highly acidic C-terminal tail**, and that removal of this motif makes Asf1 **fully cytoplasmic**, indicating the motif is **required for nuclear localization**."
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Deleting the Asf1 C-terminal cNLS reduces H3K56 acetylation when VPS75 is
present and abolishes H3K56 acetylation when VPS75 is absent, coupling nuclear
localization competence to full H3K56ac pathway output.
"deleting the Asf1 C-terminal cNLS **reduces H3K56 acetylation when VPS75 is present** and **abolishes H3K56 acetylation when VPS75 is absent**, connecting **nuclear localization competence** to **full H3K56ac pathway output**."
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In a telomere XIV-L positioning assay, an asf1 mutant shows an S-phase-specific
defect, dropping from 67.4% peripheral localization in G1 to 43.1% in S phase
(versus ~66-68% in WT).
"In a telomere XIV-L positioning assay, WT cells show ~**66.0%** peripheral localization (zone 1) in G1 and **67.5%** in S phase. In contrast, an **asf1 mutant** shows **67.4%** in G1 (n=46; p=0.05 vs WT) but drops to **43.1%** in S phase (n=51; p=4.7×10−4 vs WT), demonstrating a statistically significant **S-phase-specific defect**."
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Asf1 is required for perinuclear localization of the ETC6 chromatin domain
during interphase, and this positioning depends on Rtt109/H3K56 acetylation,
linking Asf1-mediated histone modification to higher-order chromosomal
organization.
"Asf1 is also required for **perinuclear localization of the ETC6 chromatin domain** during interphase, and this positioning depends on **Rtt109/H3K56 acetylation**, linking Asf1-mediated histone modification to higher-order chromosomal organization."
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The Asf1 C-terminal cNLS is required for full H3K56 acetylation and for
interactions with Rad53 and Hir1.
"The Asf1 C-terminal cNLS is required for full H3K56 acetylation and for interactions with Rad53 and Hir1."
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Budding-yeast Asf1 promotes H3K56 acetylation yet is dispensable for
viability/growth in S. cerevisiae, in contrast to fission yeast, while
retaining conserved chaperone and H3K56ac functions.
"Ding 2025 contrasts S. cerevisiae with fission yeast, noting Asf1 is dispensable for growth in budding yeast while retaining conserved chaperone/H3K56ac functions."