Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein.
To effectively direct targeted repression, the class I histone deacetylases (HDACs) associate with many important regulatory proteins. In this paper we describe the molecular characterization of a member of the Jumonji domain 2 (JMJD2) family of proteins, and demonstrate its binding to both class I HDACs and the retinoblastoma protein (pRb). JMJD2 proteins are characterized by the presence of two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers, one JmjN, one JmjC (containing an internal retinoblastoma-binding protein 2 (RBBP2)-like sequence), and two Tudor domains. The first member of this group, JMJD2A, is widely expressed in human tissues and cell lines, and high endogenous expression of JMJD2A mRNA was found in several cell types, including human T-cell lymphotropic virus 1 (HTLV-1)-infected cell lines. JMJD2A and JMJD2B exhibit cell type-specific responses to the HDAC inhibitor trichostatin A. We show that the JMJD2A protein associates in vivo with pRb and class I HDACs, and mediates repression of E2F-regulated promoters. In HTLV-1 virus-infected cells, we find that JMJD2A binds to the viral Tax protein. Antibodies to JMJD2A recognize the native protein but also a half-sized protein fragment, the latter up-regulated in THP-1 cells during the G(2)/M phase of the cell cycle. The ability of JMJD2A to associate with pRb and HDACs and potentiate pRb-mediated repression of E2F-regulated promoters implies an important role for this protein in cell proliferation and oncogenesis.
Gray
Steven G
SG
Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital Laboratories, Cambridge, Massachusetts 02139, USA.
Iglesias
Antonio H
AH
Lizcano
Fernando
F
Villanueva
Raul
R
Camelo
Sandra
S
Jingu
Hisaka
H
Teh
Bin T
BT
Koibuchi
Noriyuki
N
Chin
William W
WW
Kokkotou
Efi
E
Dangond
Fernando
F
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018274:Electroporation; D015723:Gene Library; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008099:Liver / Q000196:embryology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human; C494424:KDM4A protein, human; D010089:Oxidoreductases, N-Demethylating; D006655:Histone Deacetylases