Impact of neuroinflammation on epigenetic transcriptional control of Sonic Hedgehog members in the central nervous system

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Costa, Mariana Ribeiro ; Ilario dos Santos, Amanda Yasmin ; de Miranda, Tais Browne ; Aires, Rogerio ; Coque, Alex de Camargo ; Perez Hurtado, Elizabeth Cristina ; Bernardi, Maria Martha ; Arias Pecorari, Vanessa Gallego ; Andia, Denise Carleto ; Birbrair, Alexander ; Guillemin, Gilles J. ; Latini, Alexandra ; da Silva, Rodrigo A.

• Document type: Journal article
• Source: Brain Research; v. 1799, p. 15-pg., 2023-01-15.

Abstract

Sonic Hedgehog (Shh) signaling plays a critical role during central nervous system (CNS) development, and its dysregulation leads to neurological disorders. Nevertheless, little is known about Shh signaling regulation in the adult brain. Here, we investigated the contribution of DNA methylation on the transcriptional control of Shh signaling pathway members and its basal distribution impact on the brain, as well as its modulation by inflammation. The methylation status of the promoter regions of these members and the transcriptional profile of DNA-modifying enzymes (DNA Methyltransferases - DNMTs and Tet Methylcytosine Dioxygenase - TETs) were investigated in a murine model of neuroinflammation by qPCR. We showed that, in the adult brain, methylation in the CpG promoter regions of the Shh signaling pathway members was critical to determine the endogenous differential transcriptional pattern observed between distinct brain regions. We also found that neuroinflammation differentially modulates gene expression of DNA-modifying enzymes. This study reveals the basal transcriptional profile of DNMTs and TETs enzymes in the CNS and demonstrates the effect of neuroinflammation on the transcriptional control of members of the Shh Signaling pathway in the adult brain. (AU)

• FAPESP's process: 19/21392-0 - Effects of neuroinflammation on Sonic Hedgehog-mediated signaling in the central nervous system in adult mice
• Grantee: Amanda Yasmin Ilario dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/25772-2 - Participation of DNA methylation in via Hedgehog transcriptional control in a murine model of LPS-induced neuroinflammation
• Grantee: Mariana Ribeiro Costa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation