Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the β1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound PPARγ. This complex confers β-adrenergic-induced rapid JMJD1A recruitment to target sites and facilitates long-range chromatin interactions and target gene activation. This rapid gene induction is dependent on S265 phosphorylation but not on demethylation activity. Our results show that JMJD1A has two important roles in regulating hormone-stimulated chromatin dynamics that modulate thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and functions as a cAMP-responsive scaffold that facilitates long-range chromatin interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation.

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Objective-CCN3 belongs to the CCN family, which constitutes multifunctional secreted proteins that act as matrix cellular regulators. We investigated the pathophysiological roles of CCN3 in the vessels. Methods and Results-We examined the effects of CCN3 on the proliferation and migration of rat vascular smooth muscle cells (VSMC). CCN3 knockout mice were created, and vascular phenotypes and neointimal hyperplasia induced by photochemically induced thrombosis were investigated. CCN3 suppressed the VSMC proliferation induced by fetal bovine serum. The neutralizing antibody for transforming growth factor-␤ did not affect the growth inhibitory effect of CCN3. Moreover, CCN3 enhanced the mRNA expression of cyclin-dependent kinase inhibitors, p21 and p15. Gamma secretase inhibitor, an inhibitor of Notch signaling, partially inhibited the enhanced expression of p21 induced by CCN3. CCN3 also inhibited the VSMC migration. Finally, the histopathologic evaluation of the arteries 21 days after the endothelial injury revealed a 6-fold enhancement of neointimal thickening in the null mice compared with the wild-type mice. Conclusion-CCN3 See accompanying article on page 667Although other members of the CCN family, such as CCN1 and CCN2, are strongly expressed in a wide range of tissues, 6,7 CCN3 mRNA is highly and restrictively expressed in rat aortas and carotid arteries. 8 This specific expression pattern in vessels indicates that CCN3 plays an important role in vascular homeostasis. This article accompanies the DVT Series that was published in the March 2010 issue.The knockdown of CCN1/Cyr61 in mice suppresses neointimal hyperplasia in a rat artery balloon injury model. 9 CCN2/ CTGF also accumulates in the shoulders of human rupture-prone atherosclerotic plaques. 10 Because CTGF induces mononuclear cell chemotaxis in a dose-dependent manner in vitro, CTGF may also have a role in atherogenesis. However, despite the similarity of the amino acid sequence of CCN3 and CCN1 and CCN2, 4 the pathophysiological roles of CCN3 in vessels has not been fully elucidated. The present study confirmed the expression of CCN3 in medial layer of mouse aortas. Therefore, the effects of CCN3 on vascular smooth muscle cell (VSMC) proliferation and migration were investigated. Finally, CCN3-null mice were created and the physiological and pathological roles of CCN3 in vessels were determined. Materials and Methods ReagentsThe reagents used are described in the expanded Supplementary Materials and Methods section (available online at http://atvb.ahajournals.org). Cell CulturePrimary cultures of rat aortic smooth muscle cells were isolated from 250-to 300-gram Wister Rats (QLEA Japan, Inc.) as described previously. 11 See the Supplementary Materials and Methods section for details. Semiquantitative Reverse-Transcription Polymerases Chain ReactionReverse-transcription polymerase chain reaction is described in the Supplementary Materials and Methods section. Proliferation AssayVSMC proliferation was quantified by direct cell counting and by 5-bro...

Background: Polycomb repressive complex PRC1 is an epigenetic regulator of cellular differentiation. However, its function during adipogenesis is unknown. Results: FBXL10/KDM2B recruited noncanonical PRC1 complex in F-box and LRR motifs dependent on cell cycle-related genes and Pparg genes and repressed 3T3-L1 adipogenesis. Conclusion: Noncanonical PRC1 complex containing FBXL10/KDM2B regulates adipogenesis. Significance: Our findings revealed a novel epigenetic mechanism of adipogenesis.