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Advances and Prospects of Brown Adipocyte-Specific Gene PRDM16 |
Kai-xi JI1,2,Dan JIAO1,2,Zhong-kui XIE1,2,Guo YANG1,2**(),Zi-yuan DUAN3**() |
1 Northwest Institute of Eco- Environment and Resources, CAS, Lanzhou 730000, China 2 University of Chinese Academy of Sciences, Beijing 100049, China 3 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China |
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Abstract PRDM16(PR domain-containing 16) is a 16th member of PR domain family, was firstly found in a patient with leukemia and was initially thought to be related to myelodysplastic syndrome(MDS) and chronic myelogenous leukemia(CML). PRDM16 contains six important functional domains, including PR domain(PR), zinc finger domain 1(ZF-1), proximal regulatory region(PRR), repression domain(RD), zinc finger domain 2(ZF-2), and acidic activation domain(AD), respectively. The ablation of PR domain which is an exclusive domain for PRDM family has been linked to MDS and CML; the domains of ZF-1 and ZF-2 are capable to bind to peroxisome proliferator-activated receptor-α/γ(PPAR-α/γ), CCAAT-enhancer binding proteins-β(CEBP-β), peroxisome proliferator-activated receptor-γ coactivator1-α/β(PGC1-α/β) and mediator complex subunit 1(MED1); the RD domain is main site for PRDM16 to bind with C-terminal binding protein-1/2(CtBP-1/2). In mammals, the PRDM16 is involved in a spectrum of biological processes including cell fate determination and development. The PRDM16 is capable to regulate transcription via intrinsic chromatin-modifying, complexing with histone-modifying. Studies have shown the pivotal roles of PRDM16 in the determination and functions of brown and beige fat cell, as well as in thermogenesis, hematopoiesis and cardiac development. Studies indicated that PRDM16 is a key transcriptional regulator in differentiation of the brown adipocytes. PRDM16 has been found has an important role in maintaining “brown fat cell-specific” morphological properties and biological functions, as well as in association with high abundant mitochondria contents and its thermogenesis capacity. PRDM16 controls a “bidirectional cell fate switch” for skeletal myoblasts and brown fat cells. It involves in a “browning” process in white adipose tissues, which transform white adipocytes into brown/beige adipocytes. PRDM16 has also been related to the increase of visceral fat which may cause the immune response in animals. In the process of “browning”, many transcriptional factors were recruited to the promoter or enhancer regions of brown fat-related genes by regulation of PRDM16 through its ZF-1/2 domain. This, in turn, eventually promotes genes expression and BAT differentiation. And the recruit of C-terminal banding protein in the promoter of white fat cell-related genes makes them repressed by PRDM16 via its PLDLS motif in the repression domain. Recently, the genetic variations in the PRDM16 gene were identified, in humans and livestock and have been associated with a spectrum of diseases and production traits. Those reported SNPs in PRDM16 were summarized. The SNPs in human PRDM16 were significantly associated with risk of diseases such as dilated cardiomyopathy, dyslipidemia, migraine without aura and metabolic syndrome. In livestock, variations of PRDM16 have been mainly associated with growth traits and other important economic traits, including body weight, body size and carcass weight. Because of the potential applications of PRDM16 in treating human diseases and improving economic traits in livestock, the future research areas may focus on understanding the mechanism underlying the action of PRDM16 in adipose biology which may have relevance to other PRDM family members. This new knowledge may also have the potential to be exploited for therapeutic and breeding benefits.
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Received: 20 July 2018
Published: 08 May 2019
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Corresponding Authors:
Guo YANG,Zi-yuan DUAN
E-mail: yangguo@lzb.ac.cn;zyduan@genetics.ac.cn
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