Association of UHRF1 with H3K9 methylation directs the maintenance of DNA methylation

A fundamental challenge in mammalian biology has been the elucidation of mechanisms linking DNA methylation and histone post-translational modifications. Human UHRF1 (ubiquitin-like PHD and RING finger domain–containing 1) has multiple domains that bind chromatin, and it is implicated genetically in the maintenance of DNA methylation. However, molecular mechanisms underlying DNA methylation regulation by UHRF1 are poorly defined. Here we show that UHRF1 association with methylated histone H3 Lys9 (H3K9) is required for DNA methylation maintenance. We further show that UHRF1 association with H3K9 methylation is insensitive to adjacent H3 S10 phosphorylation—a known mitotic 'phospho-methyl switch'. Notably, we demonstrate that UHRF1 mitotic chromatin association is necessary for DNA methylation maintenance through regulation of the stability of DNA methyltransferase-1. Collectively, our results define a previously unknown link between H3K9 methylation and the faithful epigenetic inheritance of DNA methylation, establishing a notable mitotic role for UHRF1 in this process.

• Publication year

  2012

• Venue

  Nature Structural &Molecular Biology

• Publication date

  2012-09-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/nsmb.2391PMID 23022729PMCID 3492551
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• UHRF1 supports DNA methylation maintenance through regulation of DNA methyltransferase-1 stability.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• UHRF1 mitotic chromatin association is necessary for DNA methylation maintenance.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• UHRF1 association with H3K9 methylation is insensitive to adjacent H3 S10 phosphorylation.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• UHRF1 association with H3K9 methylation is required for maintenance of DNA methylation.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review

• dna methylation maintenance

  epigenetic process

  The process that preserves existing DNA methylation patterns during cell division and chromatin replication.

  Aliases: maintenance of DNA methylation

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• dna methyltransferase-1

  enzyme, protein

  The maintenance DNA methyltransferase responsible for copying DNA methylation patterns after replication.

  Aliases: DNMT1

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• h3k9 methylation

  epigenetic mark, histone modification

  Methylation of lysine 9 on histone H3, a chromatin mark examined for its relationship to DNA methylation maintenance.

  Aliases: methylated histone H3 Lys9, H3K9me

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• h3 s10 phosphorylation

  post-translational modification, histone modification

  Phosphorylation of serine 10 on histone H3, a neighboring histone modification considered as a mitotic chromatin signal.

  Aliases: H3S10ph

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• mitotic chromatin association

  cellular process, molecular interaction

  Association of a protein with chromatin during mitosis, when chromosomes are condensed and epigenetic marks are propagated.

  Aliases: mitotic chromatin binding

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review
• uhrf1

  protein

  A human chromatin-associated protein with ubiquitin-like, PHD, and RING finger domains studied for its role in epigenetic inheritance.

  Aliases: ubiquitin-like PHD and RING finger domain-containing 1

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) reviewKiller Whale (322360f1c1) review뀨 (7c402c1b98) reviewq (76h6bfydm6) review

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