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Epigenetic Regulation through UHRF Proteins
Author(s) -
Rothbart Scott B,
Vaughan Robert M,
Cornett Evan M,
Dickson Bradley M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.595.4
Subject(s) - dna methylation , epigenetics , chromatin , biology , histone , histone code , epigenomics , genetics , microbiology and biotechnology , computational biology , dna , gene , nucleosome , gene expression
The epigenetic inheritance of DNA methylation requires UHRF1, a histone‐ and DNA‐binding RING E3 ubiquitin ligase whose misregulation may contribute to the hallmark aberrance of DNA methylation patterning seen in cancer. UHRF1 facilitates recruitment of DNMT1 to replicating chromatin through orchestrated recognition of histones and DNA, which converge on ubiquitination of histone H3, a binding site for DNMT1. UHRF2 shares a high degree of structural homology with UHRF1, but surprisingly lacks functional redundancy as a DNA methylation regulator. Through comprehensive and comparative biochemical analysis of UHRF1 and UHRF2, we uncover mechanisms of intra‐ and inter‐molecular crosstalk regulating the binding and enzymatic activities of these chromatin regulators and reveal a molecular mechanism that uncouples UHRF2 from the DNA methylation maintenance program. Support or Funding Information This work was supported in part by the Van Andel Research Institute and a research grant from the National Institutes of Health to S.B.R. (Grant No. CA181343).