Retroviral insertional mutagenesis preferentially identifies oncogenes rather than tumor suppressor (TS) genes, presumably because a single retroviral-induced mutation is sufficient to activate an oncogene and initiate a tumor, whereas two mutations are needed to inactivate a TS gene. Here we show that TS genes can be identified by insertional mutagenesis when the screens are performed in Blm-deficient backgrounds. Blm-deficient mice, like Bloom syndrome patients, have increased frequencies of mitotic recombination owing to a mutation in the RecQ proteinlike-3 helicase gene. This increased mitotic recombination increases the likelihood that an insertional mutation in one allele of a TS gene will become homozygoused by nonsister chromatid exchange and the homozygosity of the insertion provides a marker for identifying the TS gene. We also show that known as well as novel TS genes can be identified by insertional mutagenesis in Blm-deficient mice and identify two JmjC family proteins that contribute to genome stability in species as evolutionarily diverse as mammals and Caenorhabditis elegans.

Background: NFATc1 is a necessary and sufficient transcription factor for osteoclastogenesis. Results: JMJD5 negatively regulates NFATc1 protein level through its hydroxylase activity. Conclusion: JMJD5 is a novel osteoclastogenic repressor that induces the degradation of NFATc1 protein.Significance: This study revealed a novel mechanism that regulates NFATc1 activity during osteoclastogenesis.

SUMMARYCovalent modifications of histones play an important role in chromatin architecture and dynamics. In particular, histone lysine methylation is important for transcriptional control during diverse biological processes. The nuclear protein Jmjd5 (also called Kdm8) is a histone lysine demethylase that contains a JmjC domain in the C-terminal region. In this study, we have generated Jmjd5-deficient mice (Jmjd5 MEFs. Taken together, these results suggest that Jmjd5 physiologically moderates embryonic cell proliferation through the epigenetic control of Cdkn1a expression. KEY WORDS: Jmjd5 (Kdm8), Cdkn1a, Cell proliferation, MouseJmjd5, an H3K36me2 histone demethylase, modulates embryonic cell proliferation through the regulation of Cdkn1a expression

Recent studies with avian embryos and murine embryonic stem cells have suggested that hematopoietic cells are derived from hemangioblasts, the common precursors of hematopoietic and endothelial cells. We molecularly cloned podocalyxin-like protein 1 (PCLP1) as a novel surface marker for endothelial-like cells in the aorta-gonad-mesonephros (AGM) region of mouse embryos, where long-term repopulating hematopoietic stem cells (LTR-HSCs) are known to arise. PCLP1+ CD45 cells in the AGM region incorporated acetylated low-density lipoprotein and produced both hematopoietic and endothelial cells when cocultured with OP9 stromal cells. Moreover, multiple lineages of hematopoietic cells were generated in vivo when PCLP1 +CD45-cells were injected into neonatal liver of busulfan-treated mice. Thus, PCLP1 can be used to separate hemangioblasts that give rise to LTR-HSCs.

Identification of genes involved in in vitro