TnrA is a master transcription factor regulating nitrogen metabolism in Bacillus subtilis under conditions of nitrogen limitation. When the preferred nitrogen source is in excess, feedback‐inhibited glutamine synthetase (GS) has been shown to bind TnrA and disable its activity. In cells grown with an energetically unfavorable nitrogen source such as nitrate, TnrA is fully membrane‐bound via a complex of AmtB and GlnK, which are the transmembrane ammonium transporter and its cognate regulator, respectively, originally termed NrgA and NrgB. The complete removal of nitrate from the medium leads to rapid degradation of TnrA in wild‐type cells. In contrast, in AmtB‐deficient or GlnK‐deficient strains, TnrA is neither membrane‐bound nor degraded in response to nitrate depletion. Here, we show that TnrA forms either a stable soluble complex with GlnK in the absence of AmtB, or constitutively binds to GS in the absence of GlnK. In vitro, the TnrA C‐terminus is responsible for interactions with either GS or GlnK, and this region appears also to mediate proteolysis, suggesting that binding of GlnK or GS protects TnrA from degradation. Surface plasmon resonance detection assays have demonstrated that GS binds to TnrA not only in its feedback‐inhibited form, but also in its non‐feedback‐inhibited form, although less efficiently. TnrA binding to GlnK or GS responds differentially to adenylate nucleotide levels, with ATP weakening interactions with both partners. Structured digital abstract http://www.uniprot.org/uniprot/Q45666  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 to http://www.uniprot.org/uniprot/P40758 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0107 (http://mint.bio.uniroma2.it/mint/search/interaction.do?interactionAc=MINT-8145129) http://www.uniprot.org/uniprot/P12425  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 to http://www.uniprot.org/uniprot/Q45666 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0096 (http://mint.bio.uniroma2.it/mint/search/interaction.do?interactionAc=MINT-8145196) http://www.uniprot.org/uniprot/Q45666  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 to http://www.uniprot.org/uniprot/P40758 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0096 (http://mint.bio.uniroma2.it/mint/search/interaction.do?interactionAc=MINT-8145211) http://www.uniprot.org/uniprot/Q45666  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 to http://www.uniprot.org/uniprot/P12425 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0096 (http://mint.bio.uniroma2.it/mint/search/interaction.do?interactionAc=MINT-8145181) http://www.uniprot.org/uniprot/P12425  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915 with http://www.uniprot.org/uniprot/Q45666 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006 (http://mint.bio.uniroma2.it/mint/search/interaction.do?interactionAc=MINT-8145115) http://www.uniprot.org/uniprot/P40758  http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 to http://www.uniprot....

In the chromatin of patients with Down's syndrome, changes are shown to occur in a short-term lymphocyte culture of the human peripheral blood. Some of them are induced by the patient's blood serum and are reversible when this is replaced by normal serum. A 100-fold dilution of the blood serum taken in subjects with Down's syndrome does not produce any changes in the structure of the lymphocyte chromatin of the patients. A similar procedure with the blood serum of healthy donors resulted in a drastic activation of their lymphocyte chromatin. These experiments, and investigations on the effect produced by the blood serum on the model desoxyribonucleoprotein systems, support the suggestion that the changed state of the chromatin in subjects with Down's syndrome is caused by a complex set of components contained in the blood serum, whose degree of dissociation deviates from the normal.

SUMMARY A study of the interphase chromatin structure of lymphocytes in healthy subjects, patients with Down's syndrome, and their parents and sibs was carried out by AO labelled fluorometry using our modification of DNP cell thermal denaturation. Analysis by the Sperry Univac 90/30-B computer showed that in 40 % of healthy subjects the lymphocyte chromatin melting profiles had a regularly repeated curve with six (seven) maxima at definite temperatures. In the remaining 60 % some regularly repeated deviations were present and were correlated with the sex of the subject examined. There were five subgroups in the female group and seven subgroups in the male group.In 97% of patients with Down's syndrome the lymphocyte chromatin melting profiles gave curves with three maxima at temperatures of 65, 85, and 92°C (±20). Maxima at 78 and 45°C were absent.In 80% of the mothers of probands with Down's syndrome and in 30% of female sibships, lymphocyte melting profiles also produced curves with three maxima: 65, 85, and 92°C (±20). In view of the fact that similar changes were observed in mothers and female sibs only, we propose that some women may have genotypical peculiarities which may possibly contribute to the origin of this chromosome pathology.The purpose of the investigation described here was to develop a new approach to research into the structure of the interphase chromatin in human cells. By this approach we were able to carry out a comparative analysis of the correlation between karyotype, phenotype, and genotype in healthy subjects, patients with trisomy 21, and their parents and sibs. Materials and methodsUsing a comparative analysis of temperature dependent fluorescence of acridine orange bound to cellular DNP by our modification' of the method of Ringertz and Gledhill,2 the structure of the interphase chromatin of peripheral blood lymphocytes was examined in the following groups of subjects.(I) Healthy donors: 164 subjects of whom 98 were males and 66 were females, age range 20 to 45 years.(

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