Histone demethylase JMJD5 is essential for embryonic development

Journal Article · Fri Mar 30 04:00:00 EDT 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.02.115· OSTI ID:22207781

Oh, Sangphil ^[1]; Janknecht, Ralf ^[1]

---

1. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 (United States)

Highlights: Black-Right-Pointing-Pointer Histone demethylase JMJD5 is essential for embryogenesis. Black-Right-Pointing-Pointer Transcription of tumor suppressor p53 is upregulated in JMJD5 knockout embryos. Black-Right-Pointing-Pointer JMJD5 may antagonize p53-dependent growth inhibition and apoptosis. Black-Right-Pointing-Pointer JMJD5 is overexpressed in leukemias and breast cancer. -- Abstract: Histone lysine methylation is pivotal in regulating chromatin structure and thus profoundly affects the transcriptome. JMJD5 (jumonji C domain-containing 5) is a histone demethylase that specifically removes methyl moieties from dimethylated lysine 36 on histone H3 and exerts a pro-proliferative effect on breast cancer cells. Here, we generated JMJD5 knockout mice in order to study the physiological significance of this enzyme. Whereas heterozygous knockout mice displayed no overt phenotype, homozygous JMJD5 knockouts died around day 10 of embryonal development. JMJD5{sup -/-} embryos showed delayed development already at E8.5 and were actively resorbed at E10.5. While strong JMJD5 expression was observed only in the yolk sac at E8.5, JMJD5 was robustly expressed in E10.5 embryos at several sites, including the heart and eye. Lack of JMJD5 resulted in transcriptional upregulation of the tumor suppressor p53. Concurrently, the cell cycle inhibitor p21 and the pro-apoptotic molecule Noxa, both of which are prominent p53 target genes, became strongly upregulated in JMJD5{sup -/-} embryos. Collectively, our data indicate that JMJD5 is essential during embryonal development and a repressor of p53 expression. The latter suggests that JMJD5 has oncogenic activity and accordingly JMJD5 is upregulated in leukemias and breast cancer.

• OSTI ID: 22207781
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 420; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
CHROMATIN
EMBRYOS
GALACTOSIDASE
GENES
HEART
KNOCK-OUT REACTIONS
LEUKEMIA
LYSINE
MAMMARY GLANDS
METHYLATION
MICE
MONOCLINIC LATTICES
NEOMYCIN
ONTOGENESIS
PHENOTYPE
TRANSCRIPTION