JAZF1

Official Full Name

JAZF zinc finger 1

Organism

Homo sapiens

GeneID

221895

Background

This gene encodes a nuclear protein with three C2H2-type zinc fingers, and functions as a transcriptional repressor. Chromosomal aberrations involving this gene are associated with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized [provided by RefSeq, Jul 2008]

Synonyms

TIP27; ZNF802;

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Detailed Information

Recent Research

JAZF1 is also referred to as Tip27 and ZNF802 (molecular weight of coding protein is 27 KDa and its isoelectric point is 8.83). In fact, JAZF1 is a newly identified gene with unknown function. Some reports show that JAZF1 is the co-repressor for nuclear orphan receptor TAK1. Moreover, a recent study has shown that JAZF1 is related to prostate cancer, endometrial stromal tumor, but its function and specific pathogenit mechanisms of these diseases remain unclear. The JAZF1 polymorphism (rs864745) is within intron 1 of this gene, which interacts specifically with the ligand binding domain of TR4 and functions as a TR4-selective cofactor that may be involved in mediation transcriptional repression by TR4. The rs864745 variant in JAZF1 gene may act as genetic risk factors for the development of type 2 diabetes mellitus (T2DM) in a Saudi population.

JAZF1 may have a role as a tumor suppressor gene. Some studies show that JAZF1/SUZ12 fusion is present only in a subset of primary ESTs. Two zinc finger domains in JAZF1 gene show homology to the yeast protein Sfp1p, which negatively regulates the G2/M transition in Streptomyces cerevisiae by transcriptional activation of some other genes like PDS1 and Esp1p. JAZF1/SUZ12 fusion is frequently but not consistently present in ESNs and in ESTs of classic histology and less often in other histological subtypes. Indeed, some reports suggest that JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. SREDPI exhibited an inhibitory function on the expression of JAZF1. When the expression of JAZF1 was downregulated, the contents of red lipid droplets and triglyceride in the cytoplasm significantly increased. The rs864745 variant in JAZF1 and rs7961581 variant in TSPAN8/LGR5 are significantly associated with insulin secretion and glucose-tolerance and T2DM risk. SREDP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes.

JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARβ/δ signaling. The JAZF1/SUZ12 gene fusion is suggested to become a specific diagnostic tool, especially in difficult borderline cases. The JAZF1/SUZ12 fusion could be used to differentiate between LG-ESS and HG-ESS. Furthermore, studies concerning the JAZF1/SUZ12 gene fusion in different ESS variants are rare. JAZF1 is associated with TSPAN8/LGR5 variants in relation to T2DM in a Saudi population. Some reports show that JAZF1 and TSPAN8/LGR5 affect various aspects of β-cell function. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. JAZF1 significantly reduced the amount of red lipid droplets in the cytoplasm of adipocytes, and the triglyceride content was reduced significantly. Some reports show that the presence of the JAZF1/SUZ12 fusion in one case of endometrial stromal nodule (ESN) with smooth muscle (SM) differentiation. The JAZF1/SUZ12 chimeric protein might disrupt transcription in lineage-specific manner. The loss of expression of a normal JAZF1 has been shown in some ESS cases. JAZF1 could be closely related to glycolipid metabolism. JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. The variant of JAZF1 is associated with lower birth weight, which is one of the high risk factors for T2DM. JAZF1 is a transcriptional repressor of TAK1, which indirectly suggests that JAZF1 is related to gluconeogenesis and insulin sensitivity. Therefore, JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

References:

Ming G F, et al. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes. Biochemical & Biophysical Research Communications, 2014, 445(3):673-680.
Alharbi K K, et al. Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population. Diabetology& Metabolic Syndrome, 2015, 7(1):92.
Ma X, Wang J, et al. The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis. Oncotarget, 2016, 8(3).
Ueyama M, et al. The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus. Journal of Gastroenterology, 2016, 51(4):370.

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