Identification of Jmjd3 as an Essential Epigenetic Regulator of Hox Gene Temporal Collinear Activation for Body Axial Patterning in Mice

Body axial patterning develops via a rostral-to-caudal sequence and relies on the temporal colinear activation of Hox genes. However, the underlying mechanism of Hox gene temporal colinear activation remains largely elusive. Here, with small-molecule inhibitors and conditional gene knockout mice, we identified Jmjd3, a subunit of TrxG, as an essential regulator of temporal colinear activation of Hox genes with its H3K27me3 demethylase activity. We demonstrated that Jmjd3 not only initiates but also maintains the temporal collinear expression of Hox genes. However, we detected no antagonistic roles between Jmjd3 and Ezh2, a core subunit of PcG repressive complex 2, during the processes of axial skeletal patterning. Our findings provide new insights into the regulation of Hox gene temporal collinear activation for body axial patterning in mice.

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Shengjie Tongyu Granule Inhibits Vascular Remodeling in ApoE-Gene-Knockout Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/897875 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13

Author(s):

Min Chen ◽

Wenli Cheng ◽

Zaixiang Shi ◽

Nishihara Tatsukazu ◽

Tongliang Zhou ◽

...

Keyword(s):

Knockout Mice ◽

Vascular Remodeling ◽

Gene Knockout ◽

Elastic Fiber ◽

Underlying Mechanism ◽

Inhibitory Effect ◽

Apoe Gene ◽

Control Group ◽

Gene Knockout Mice ◽

Grade Ii

The aim of the present paper was to investigate the effect of Shengjie Tongyu granule on vascular remodeling in atherosclerotic mice and the relevant underlying mechanism. Sixty male ApoE-gene-knockout mice, fed a high-fat diet from 6 weeks of age, were randomized into a Shengjie Tongyu granule group (4.00 g/kg/d), a simvastatin group (9.01 mg/kg/d), and a control group (normal saline: 0.2 mL/d). At the ages of 30 and 40 weeks, we sacrificed the mice for various measurements. The results show that treatment with Shengjie Tongyu granule and simvastatin significantly decreased lumen and plaque areas in the aortic root at 30 and 40 weeks of age, decreased grade II elastic fiber lesions in the ascending aorta at 30 weeks of age, and decreased both grade II and III lesions at 40 weeks of age, compared to controls. The content of superoxide anions, and expression of MOMA-2, plasma ICAM-1, and NFκB p50 in 30- and 40-week-old mice in the Shengjie Tongyu granule and simvastatin groups were also significantly reduced compared to the control group. In conclusion, Shengjie Tongyu granule has a clear inhibitory effect on vascular remodeling and on inflammatory pathways in ApoE-gene-knockout mice.

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Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo

10.1101/2021.09.08.459528 ◽

2021 ◽

Author(s):

Natalia Benetti ◽

Quentin Gouil ◽

Andres Tapia del Fierro ◽

Tamara Beck ◽

Kelsey Breslin ◽

...

Keyword(s):

Gene Expression ◽

Maternal Effect ◽

Normal Development ◽

Preimplantation Embryo ◽

Epigenetic Silencing ◽

Hox Gene ◽

Skeletal Patterning ◽

Epigenetic Effects ◽

Epigenetic Regulator ◽

Maternal Effect Genes

AbstractParents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect on Hox gene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation of Hox genes postimplantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo. Hox genes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not alter these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriate Hox gene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype.

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Study about the Expression of CypA Proteins and Its Blocking Effect in the Cerebellum from FMR1 Gene Knockout Mice by Electroacupuncture of DU1 Acupoint

Rehabilitation Medicine ◽

10.3724/sp.j.1329.2017.05029 ◽

2017 ◽

Vol 27 (5) ◽

pp. 29

Author(s):

Dong LIN ◽

Wanping BU ◽

Xiaoting YANG

Keyword(s):

Knockout Mice ◽

Gene Knockout ◽

Blocking Effect ◽

Fmr1 Gene ◽

Gene Knockout Mice

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Detrimental implication of B1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

International Immunopharmacology ◽

10.1016/s1567-5769(02)00022-x ◽

2002 ◽

Vol 2 (6) ◽

pp. 815-822 ◽

Cited By ~ 47

Author(s):

Caroline Lagneux ◽

Michael Bader ◽

João B. Pesquero ◽

Pierre Demenge ◽

Christophe Ribuot

Keyword(s):

Myocardial Ischemia ◽

Knockout Mice ◽

Gene Knockout ◽

B1 Receptors ◽

Gene Knockout Mice ◽

Pharmacological Blockade

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Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice

Neuropharmacology ◽

10.1016/j.neuropharm.2006.05.003 ◽

2006 ◽

Vol 51 (3) ◽

pp. 612-622 ◽

Cited By ~ 27

Author(s):

Jalal Izadi Mobarakeh ◽

Kazuhiro Takahashi ◽

Shinobu Sakurada ◽

Atsuo Kuramasu ◽

Kazuhiko Yanai

Keyword(s):

Knockout Mice ◽

Gene Knockout ◽

Receptor Gene ◽

Histamine H2 Receptor ◽

H2 Receptor ◽

Antinociceptive Effects ◽

Gene Knockout Mice

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Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)30162-0 ◽

2002 ◽

Vol 43 (2) ◽

pp. 205-214 ◽

Cited By ~ 3

Author(s):

Brett Garner ◽

David A. Priestman ◽

Roland Stocker ◽

David J. Harvey ◽

Terry D. Butters ◽

...

Keyword(s):

Apolipoprotein E ◽

Knockout Mice ◽

Gene Knockout ◽

E Gene ◽

Apolipoprotein E Gene ◽

Gene Knockout Mice

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The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice

Biomedicines ◽

10.3390/biomedicines9070840 ◽

2021 ◽

Vol 9 (7) ◽

pp. 840

Author(s):

Qiaofeng Zhao ◽

Satoshi Koyama ◽

Nagisa Yoshihara ◽

Atsushi Takagi ◽

Etsuko Komiyama ◽

...

Keyword(s):

Alopecia Areata ◽

Gene Knockout ◽

Stress Test ◽

Coiled Coil ◽

Risk Haplotype ◽

Gene Expression Microarray ◽

Wild Type ◽

Gene Knockout Mice ◽

Deficient Mice ◽

Gene Expression Microarray Analysis

We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype. We also reported that the engineered mice with this risk allele exhibited. To investigate more about the involvement of the CCHCR1 gene in AA pathogenesis, we developed an AA model using C57BL/6N cchcr1 gene knockout mice. In this study, mice (6–8 weeks) were divided into two groups: cchcr1−/− mice and wild-type (WT) littermates. Both groups were subjected to a water avoidance stress (WAS) test. Eight weeks after the WAS test, 25% of cchcr1−/− mice exhibited non-inflammatory foci of alopecia on the dorsal skin. On the other hand, none of wild-type littermates cause hair loss. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings. Additionally, gene expression microarray analysis of cchcr1−/− mice revealed abnormalities of hair related genes compared to the control. Our results strongly suggest that CCHCR1 is associated with AA pathogenesis and that cchcr1−/− mice are a good model for investigating AA.

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