000162309 001__ 162309 000162309 005__ 20251017144607.0 000162309 0247_ $$2doi$$a10.1128/msystems.00373-25 000162309 0248_ $$2sideral$$a144918 000162309 037__ $$aART-2025-144918 000162309 041__ $$aeng 000162309 100__ $$0(orcid)0000-0002-0474-255X$$aGuío, J. 000162309 245__ $$aRegulatory networks of FUR and NtcA are intertwined by transcriptional regulators, two-component systems, serine/threonine kinases, and sigma factors in Anabaena sp. PCC 7120 000162309 260__ $$c2025 000162309 5060_ $$aAccess copy available to the general public$$fUnrestricted 000162309 5203_ $$aFUR proteins in Anabaena sp. PCC 7120 (FurA/Fur, FurB/Zur, and FurC/PerR) are a family of transcriptional regulators involved in the control of highly important metabolic processes such as the maintenance of metal homeostasis, the regulation of oxidative stress response, and the adaptation to nitrogen starvation. Previous RNAseq analyses of FUR misregulation strains revealed a broad panel of genes directly modulated by these transcriptional regulators. However, the expression of several regulatory proteins was also altered, indicating that FUR proteins could extend their influence by exerting a second level of regulation through some members of their regulons. In this work, by combining differential gene expression data and electrophoretic mobility shift assays (EMSAs), we sought to identify novel direct targets of FUR proteins with regulatory functions, namely, transcriptional regulators, two-component systems, sigma factors, and other proteins with regulatory functions such as serine/threonine kinases. This allowed us to build a network composed of these regulatory proteins that are directly modulated by FUR proteins. In addition, taking into account the role of FUR proteins in the regulation of nitrogen metabolism, the overlap between FUR and NtcA regulatory networks was studied, revealing that an important part of the FUR network is coregulated by NtcA. These results unveil a complex network in Anabaena in which regulatory proteins hierarchically below FUR or NtcA proteins could be controlling the expression of several genes, connecting the integration of stress signaling performed by FUR and NtcA to a wide set of cyanobacterial transcriptional responses. 000162309 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E35-20R$$9info:eu-repo/grantAgreement/ES/MCIU/PID2019-104889GB-I00 000162309 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es 000162309 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000162309 700__ $$0(orcid)0000-0002-2742-3711$$aPeleato, M. L. 000162309 700__ $$0(orcid)0000-0001-8644-4574$$aFillat, M. F.$$uUniversidad de Zaragoza 000162309 700__ $$0(orcid)0000-0001-6435-3540$$aSevilla, E.$$uUniversidad de Zaragoza 000162309 7102_ $$11002$$2412$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Fisiología Vegetal 000162309 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000162309 773__ $$g10, 7 (2025), e00373-25 [21 pp.]$$pmSystems$$tmSystems$$x2379-5077 000162309 8564_ $$s2410373$$uhttps://zaguan.unizar.es/record/162309/files/texto_completo.pdf$$yVersión publicada 000162309 8564_ $$s2270218$$uhttps://zaguan.unizar.es/record/162309/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000162309 909CO $$ooai:zaguan.unizar.es:162309$$particulos$$pdriver 000162309 951__ $$a2025-10-17-14:15:50 000162309 980__ $$aARTICLE