PHF20 Readers Link Methylation of Histone H3K4 and p53 with H4K16 Acetylation
Brianna J. Klein,
Xiaoyan Wang,
Gaofeng Cui,
Chao Yuan,
Maria Victoria Botuyan,
Kevin Lin,
Yue Lu,
Xiaolu Wang,
Yue Zhao,
Christiane J. Bruns,
Georges Mer,
Xiaobing Shi,
Tatiana G. Kutateladze
Affiliations
Brianna J. Klein
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Xiaoyan Wang
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Gaofeng Cui
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
Chao Yuan
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Maria Victoria Botuyan
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
Kevin Lin
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yue Lu
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xiaolu Wang
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yue Zhao
Department of General, Visceral and Tumor Surgery, University Clinic Cologne, Cologne 50931, Germany
Christiane J. Bruns
Faculty of Medicine, Ludwig Maximilian University of Munich, Munich 80336, Germany
Georges Mer
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
Xiaobing Shi
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Tatiana G. Kutateladze
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first)-NSL (non-specific lethal) that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD) finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents an example of a native reader that selects for this modification. Biochemical and structural analyses help to explain this selectivity and the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a unique PHF20-mediated link between MOF histone acetyltransferase (HAT), p53, and H3K4me2, and suggest a model for rapid spreading of H4K16ac-enriched open chromatin.
