Here we describe two mammalian transcription factors selectively expressed in the central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been isolated and sequenced. RNA blotting assays demonstrated the selective presence of NPAS1 and NPAS2 mRNAs in brain and spinal cord tissues of adult mice. NPAS1 mRNA was first detected at embryonic day 15 of mouse development, shortly after early organogenesis of the brain. NPAS2 mRNA was first detected during early postnatal development of the mouse brain. In situ hybridization assays using brain tissue of postnatal mice revealed an exclusively neuronal pattern of expression for NPAS1 and NPAS2 mRNAs. The human NPAS1 gene was mapped to chromosome 19q13.2-q13.3, and the mouse Npas1 gene to chromosome 7 at 2 centimorgans. Similarly, the human NPAS2 gene was assigned to chromosome 2p11.2-2q13, and the mouse Npas2 gene to chromosome 1 at 21-22 centimorgans. The chromosomal regions to which human NPAS1 and NPAS2 map are syntenic with those containing the mouse Npas1 and Npas2 genes, indicating that the mouse and human genes are true homologs.Molecular biological studies reported during the past decade have identified a family of transcription factors designated basic helix-loop-helix (bHLH)-PAS proteins. Members of this protein family contain a bHLH DNA binding domain located on the amino-terminal side of a PAS domain. PAS is an acronym derived from the initial three proteins observed to contain this polypeptide motif: the period gene product of fruit flies (1-3), the aryl hydrocarbon receptor nuclear transporter (4), and the single-minded gene product of fruit flies (5). The PAS domain is approximately 260 amino acids in length and contains two direct repeats of about 60 amino acids (5).Biochemical studies of the aryl hydrocarbon (AH) receptor have provided evidence that it is directly regulated by xenobiotic compounds (reviewed in ref. 6). In its resting state, the AH receptor is retained in the cytoplasm in association with heat shock protein 90 (HSP90) (7). Upon exposure to xenobiotics, the AH receptor is released from HSP90 and dimerizes with the AH receptor nuclear transporter, a second bHLH-PAS domain protein critical to the function of the AH receptor (4, 8). The activated AH receptor͞AH receptor nuclear transporter heterodimer enters the nucleus and activates a battery of genes, including those encoding P450 enzymes that facilitate detoxification (9, 10). The PAS domain of the AH receptor performs three biochemical functions in this regulatory path-

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To elucidate the molecular features of active chromatin, we have mapped, by two-dimensional electrophoresis, the protein composition of nucleosomes that package the immunoglobulin K chain gene of mouse plasmacytoma cells. Nucleoprotein particles that possess the active K chain gene comigrate with bulk mononucleosomes that contain high mobility group proteins HIMG-14 or -17 but lack histone HI. High electrophoretic resolution of the underlying core particles, after removal of ubiquitin by isopeptidase treatment, reveals that these nucleosomes are nonubiquitinated, even though they coincidently migrate with bulk ubiquitinated particles. This distinctive electrophoretic behavior may be correlated with the presence of histone H2A.X. Nucleosomes exhibiting these unusual properties appear to span at least 10 kilobases, in both transcribed and nontranscribed regions, suggesting that mechanismns independent of transcription exist to initiate, maintain, and propagate a common chromatin phenotype over long distances along the K chain locus.The protein compositions and nucleoprotein structures that generate productive templates for RNA polymerase II in living cells are currently unknown. In vitro the histones strongly inhibit transcription (1), yet the results of experiments employing immunoelectron microscopy (2), microinjection of antibodies (3), and nuclease digestion (4-6) suggest that nucleosomes are present on many transcriptionally active class II genes in vivo.It is generally believed that nucleosomes within transcribed regions possess special features that permit RNA polymerase access and passage.