TY - JOUR
T1 - Impact of neuroinflammation on epigenetic transcriptional control of Sonic Hedgehog members in the central nervous system
AU - Costa, Mariana Ribeiro
AU - dos Santos, Amanda Yasmin Ilario
AU - de Miranda, Taís Browne
AU - Aires, Rogério
AU - de Camargo Coque, Alex
AU - Hurtado, Elizabeth Cristina Perez
AU - Bernardi, Maria Martha
AU - Pecorari, Vanessa Gallego Arias
AU - Andia, Denise Carleto
AU - Birbrair, Alexander
AU - Guillemin, Gilles J.
AU - Latini, Alexandra
AU - da Silva, Rodrigo A.
PY - 2023/1/15
Y1 - 2023/1/15
N2 - 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.
AB - 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.
KW - DNA methylation
KW - DNA-modifying
KW - Neuroepigenetics
KW - Neuroinflammation
KW - Sonic Hedgehog
KW - SUFU hypermethylation
UR - http://www.scopus.com/inward/record.url?scp=85143138626&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2022.148180
DO - 10.1016/j.brainres.2022.148180
M3 - Article
C2 - 36463954
AN - SCOPUS:85143138626
SN - 0006-8993
VL - 1799
SP - 1
EP - 15
JO - Brain Research
JF - Brain Research
M1 - 148180
ER -