162309 20251017144607.0 doi 10.1128/msystems.00373-25 sideral 144918 ART-2025-144918 eng Guío, J. (orcid)0000-0002-0474-255X Regulatory networks of FUR and NtcA are intertwined by transcriptional regulators, two-component systems, serine/threonine kinases, and sigma factors in Anabaena sp. PCC 7120 2025 Access copy available to the general public Unrestricted FUR proteins in Anabaena sp. PCC 7120 (FurA/Fur, FurB/Zur, and FurC/PerR) are a family of transcriptional regulators involved in the control of highly important metabolic processes such as the maintenance of metal homeostasis, the regulation of oxidative stress response, and the adaptation to nitrogen starvation. Previous RNAseq analyses of FUR misregulation strains revealed a broad panel of genes directly modulated by these transcriptional regulators. However, the expression of several regulatory proteins was also altered, indicating that FUR proteins could extend their influence by exerting a second level of regulation through some members of their regulons. In this work, by combining differential gene expression data and electrophoretic mobility shift assays (EMSAs), we sought to identify novel direct targets of FUR proteins with regulatory functions, namely, transcriptional regulators, two-component systems, sigma factors, and other proteins with regulatory functions such as serine/threonine kinases. This allowed us to build a network composed of these regulatory proteins that are directly modulated by FUR proteins. In addition, taking into account the role of FUR proteins in the regulation of nitrogen metabolism, the overlap between FUR and NtcA regulatory networks was studied, revealing that an important part of the FUR network is coregulated by NtcA. These results unveil a complex network in Anabaena in which regulatory proteins hierarchically below FUR or NtcA proteins could be controlling the expression of several genes, connecting the integration of stress signaling performed by FUR and NtcA to a wide set of cyanobacterial transcriptional responses. info:eu-repo/grantAgreement/ES/DGA/E35-20R info:eu-repo/grantAgreement/ES/MCIU/PID2019-104889GB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Peleato, M. L. (orcid)0000-0002-2742-3711 Fillat, M. F. Universidad de Zaragoza (orcid)0000-0001-8644-4574 Sevilla, E. Universidad de Zaragoza (orcid)0000-0001-6435-3540 1002 412 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Fisiología Vegetal 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 10, 7 (2025), e00373-25 [21 pp.] mSystems mSystems 2379-5077 2410373 http://zaguan.unizar.es/record/162309/files/texto_completo.pdf Versión publicada 2270218 http://zaguan.unizar.es/record/162309/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:162309 articulos driver 2025-10-17-14:15:50 ARTICLE