High impact information on Nnat

• Northern blot and in situ hybridization analysis of WT and KO samples confirmed the downregulation of Nnat in pancreas of mutant BETA2 embryos [1].
• Peg5/Neuronatin is an imprinted gene located on sub-distal chromosome 2 in the mouse [2].
• Using modified BAC transgenes, we show that imprinted expression of Nnat at ectopic sites requires, at most, an 80-kb region around the gene [3].
• Imprinted expression of neuronatin from modified BAC transgenes reveals regulation by distinct and distant enhancers [3].
• More detailed mapping analysis of Nnat showed that it is located between the T26H and T2Wa translocation breakpoints which is, surprisingly, proximal to the reported imprinting region between the T2Wa and T28H translocation breakpoints, suggesting that there may be two distinct imprinting regions on distal chromosome 2 [4].

Biological context of Nnat

• Nnat maps to distal chromosome (Chr) 2, which contains an imprinting region that causes morphological abnormalities and early neonatal lethality [4].
• The differential expression of Nnat was supported by DNA methylation analysis with the paternally inherited alleles being unmethylated and the maternal alleles fully methylated [4].
• Nnat has been excluded as a candidate for either or both the behavioural phenotypes as it lies proximal to the 2H3-2H4 imprinting region [5].
• Collectively, the data indicate that Nnat enhances CREB phosphorylation through increasing intracellular free calcium levels, which potentiates expression of adipogenic transcription factors resulting in heightened adipocyte differentiation [6].
• Here, we examined the expression of Nnat in adipose tissue and demonstrated that the ectopic expression of Nnat mediated by retroviral infection or stable transfection of 3T3-L1 pre-adipocytes stimulated differentiation into mature adipocytes with early induction of adipogenic transcription factors [6].

Anatomical context of Nnat

• Neuronatin (Nnat) is a recently identified paternally expressed imprinted gene that is initially expressed in the rhombomeres and pituitary gland and later more widely in the central and peripheral nervous system mainly in postmitotic and differentiating neuroepithelial cells [4].
• Also significant is the observation that Nnat is imprinted by the blastocyst stage of development although the other genes are not, indicating a temporal imprinting program [7].
• However, Nnat also appears to be abundantly expressed in adipose tissue, and is conspicuously elevated in the adipose tissue of obese Zucker diabetic fatty rats compared with control lean Zucker lean control rats shown in our previous report [6].
• Moreover, in 3T3-L1 cells overexpressing Nnat, increased intracellular free calcium levels and enhanced phosphorylation of cAMP-response element-binding protein (CREB) were observed, which appears to potentiate CCAAT/enhancer-binding protein (C/EBP)beta, C/EBPdelta, and C/EBPalpha transcriptional activities [6].
• Segment-specific expression of the neuronatin gene during early hindbrain development [8].

Other interactions of Nnat

• Western blot analysis of the mouse brain showed reduced levels of calpastatin and rabaptin-5 and higher amount of neuronatin in PKU compared to the wild type [9].
• Neuronatin and 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) reportedly have role in memory [9].
• Sites of imprinted methylation were also detected at the loci for neuronatin on Chr 2 and for M-cadherin on Chr 8 [10].
• These, in addition to two other genes, neuronatin and PB cadherin, which were up- and down-regulated, respectively, showed a more rapid response to TH than the cell cycle regulators and may represent direct targets of TH [11].

References