Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation.
Distinct lysine methylation marks on histones create dynamic signatures deciphered by the "effector" modules, although the underlying mechanisms remain unclear. We identified the plant homeodomain- and Jumonji C domain-containing protein PHF2 as a novel histone H3K9 demethylase. We show in biochemical and crystallographic analyses that PHF2 recognizes histone H3K4 trimethylation through its plant homeodomain finger and that this interaction is essential for PHF2 occupancy and H3K9 demethylation at rDNA promoters. Our study provides molecular insights into the mechanism by which distinct effector domains within a protein cooperatively modulate the "cross-talk" of histone modifications.
Departments of Biochemistry and Molecular Biology, Houston, Texas 77030; Centers for Cancer Epigenetics, Houston, Texas 77030; Stem Cell and Developmental Biology, Houston, Texas 77030.
Hong
H
Wen
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35205.
Jingzhi
J
Li
Departments of Biochemistry and Molecular Biology, Houston, Texas 77030; Centers for Cancer Epigenetics, Houston, Texas 77030; Stem Cell and Developmental Biology, Houston, Texas 77030.
Tanjing
T
Song
Departments of Biochemistry and Molecular Biology, Houston, Texas 77030.
Ming
M
Lu
Centers for Cancer Epigenetics, Houston, Texas 77030; Molecular and Cellular Oncology, Houston, Texas 77030.
Pu-Yeh
PY
Kan
Centers for Cancer Epigenetics, Houston, Texas 77030; Molecular and Cellular Oncology, Houston, Texas 77030.
Min Gyu
MG
Lee
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35205.
Bingdong
B
Sha
Departments of Biochemistry and Molecular Biology, Houston, Texas 77030; Centers for Cancer Epigenetics, Houston, Texas 77030; Stem Cell and Developmental Biology, Houston, Texas 77030; Genes and Development Graduate Program, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030. Electronic address: xbshi@mdanderson.org.
Xiaobing
X
Shi
D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods; D004275:DNA, Ribosomal / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D004275:DNA, Ribosomal; D006657:Histones; D018398:Homeodomain Proteins; C117905:PHF2 protein, human; D010455:Peptides; D010940:Plant Proteins; D049452:Green Fluorescent Proteins