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Histone Acetyl Transferase (HAT) HBO1 and PHD Finger Protein 17 (PHF17/JADE1) in Epithelial Cell Regeneration
Author(s) -
Panchenko Maria,
Havasi Andrea,
Haegele Joseph,
Bonegio Ramon,
Ichimura Takaharu,
Siriwardairodhini,
Gall Jonathan
Publication year - 2013
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.27.1_supplement.772.2
Subject(s) - histone , acetylation , histone h4 , cell growth , chromatin , biology , histone h3 , microbiology and biotechnology , cell cycle , cancer research , cell , dna , gene , biochemistry
HBO1 acetylates lysine residues of histones and is involved in DNA replication and gene transcription. Two isoforms of JADE1, JADE1S and JADE1L, bind HBO1 and promote acetylation of chromatinal histones. We characterized the role of JADE1‐HBO1 complexes in vitro and in vivo during epithelial cell replication. Downregulation of JADE1 by siRNA diminished the rate of DNA synthesis in cultured cells, decreased endogenous HBO1 protein expression, and prevented chromatin recruitment of replication factor Mcm7, demonstrating that JADE1 is required for cell proliferation. We used a murine model of acute kidney injury (AKI) to examine expression of HBO1‐JADE1S/L in injured and regenerating epithelial tissue. In control kidneys, JADE1S, JADE1L, and HBO1 were expressed in nuclei of proximal and distal tubular epithelial cells. Ischemia and reperfusion injury resulted in an initial decrease in JADE1S, JADE1L, and HBO1 protein levels which returned to the baseline during renal recovery. HBO1 and JADE1S recovered as cell proliferation reached its maximum while JADE1L recovered after bulk proliferation had ceased. The temporal expression of JADE1S correlated with the acetylation of histone H4 on lysine 5 and 12, but not with acetylation of histone H3 on lysine 14, demonstrating that the JADE1S‐HBO1 complex specifically marks H4 during epithelial cell proliferation. These data implicated JADE1‐HBO1 complex in AKI and suggested distinct roles for JADE1 isoforms during epithelial cells recovery. NIH RO1 DK087910 , and ACS IRG‐72–001‐32 (to M. V. P.). NIH 1KO8DK090143 (to A.H.).