Anti-DLG4 monoclonal antibody, clone 8F4 [Biotin]

We have determined the cDNA sequence, expression pattern, and chromosomal location of the human gene DLG4, encoding the postsynaptic density-95 (PSD95) protein. hPSD95 is a 723-amino-acid protein that is 99% identical to its rodent counterparts. This is the fourth human protein identified as showing significant similarity to the Drosophila tumor suppressor Dig. These proteins constitute the DLG; subfamily of the membrane-associated guanylate kinase protein family. The expression of DLG4 in neural tissue is consistent with the pattern observed for its rat homolog. However, DLG4 is also expressed in a wide range of nonneural tissues, suggesting that the protein may have additional roles in humans. Using radiation-hybrid mapping panels, we mapped the DLG4 locus to 17p13.1, a region associated with several diseases, the phenotypes of which are consistent with loss of PSD95 function. (C) 1997 Academic Press.

Sleep is critical for normal brain function and mental health. However, the molecular mechanisms mediating the impact of sleep loss on both cognition and the sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain gene expression broadly. These data contributed to current hypotheses regarding the role for sleep in metabolism, synaptic plasticity and neuroprotection. These changes in gene expression likely underlie increased sleep intensity following sleep deprivation (SD). Here we tested the hypothesis that epigenetic mechanisms coordinate the gene expression response driven by SD. We found that SD altered the cortical genome-wide distribution of two major epigenetic marks: DNA methylation and hydroxymethylation. DNA methylation differences were enriched in gene pathways involved in neuritogenesis and synaptic plasticity, whereas large changes (>4000 sites) in hydroxymethylation where observed in genes linked to cytoskeleton, signaling and neurotransmission, which closely matches SD-dependent changes in the transcriptome. Moreover, this epigenetic remodeling applied to elements previously linked to sleep need (for example, Arc and Egr1) and synaptic partners of Neuroligin-1 (Nlgn1; for example, Dlg4, Nrxn1 and Nlgn3), which we recently identified as a regulator of sleep intensity following SD. We show here that Nlgn1 mutant mice display an enhanced slow-wave slope during non-rapid eye movement sleep following SD but this mutation does not affect SD-dependent changes in gene expression, suggesting that the Nlgn pathway acts downstream to mechanisms triggering gene expression changes in SD. These data reveal that acute SD reprograms the epigenetic landscape, providing a unique molecular route by which sleep can impact brain function and health.