Upregulation of TET1 and Downregulation of APOBEC3A and APOBEC3C in the Parietal Cortex of Psychotic Patients
Overview
Public Health
Affiliations
Increasing evidence suggests that epigenetic dysfunction may account for the alteration of gene transcription present in neuropsychiatric disorders such as schizophrenia (SZ), bipolar disorder (BP) and autism. Here, we studied the expression of the ten-eleven translocation (TET) gene family and activation-induced deaminase/apolipoprotein B mRNA-editing enzymes (AID/APOBEC) in the inferior parietal lobule (IPL) (BA39-40) and the cerebellum of psychotic (PSY) patients, depressed (DEP) patients and nonpsychiatric (CTR) subjects obtained from the Stanley Foundation Neuropathology Consortium Medical Research Institute. These two sets of enzymes have a critical role in the active DNA demethylation pathway. The results show that TET1, but not TET2 and TET3, mRNA and protein expression was increased (two- to threefold) in the IPL of the PSY patients compared with the CTR subjects. TET1 mRNA showed no change in the cerebellum. Consistent with the increase of TET1, the level of 5-hydroxymethylcytosine (5hmC) was elevated in the IPL of PSY patients but not in the other groups. Moreover, higher 5hmC levels were detected at the glutamic acid decarboxylase67 (GAD67) promoter only in the PSY group. This increase was inversely related to the decrease of GAD67 mRNA expression. Of 11 DNA deaminases measured, APOBEC3A mRNA was significantly decreased in the PSY and DEP patients, while APOBEC3C was decreased only in PSY patients. The other APOBEC mRNA studied failed to change. Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight the possible role of altered DNA demethylation mechanisms in the pathophysiology of psychosis.
Methods for Detection and Mapping of Methylated and Hydroxymethylated Cytosine in DNA.
Kisil O, Sergeev A, Bacheva A, Zvereva M Biomolecules. 2024; 14(11).
PMID: 39595523 PMC: 11591845. DOI: 10.3390/biom14111346.
TET enzyme driven epigenetic reprogramming in early embryos and its implication on long-term health.
Montgomery T, Uh K, Lee K Front Cell Dev Biol. 2024; 12:1358649.
PMID: 39149518 PMC: 11324557. DOI: 10.3389/fcell.2024.1358649.
Huang M, Wang J, Liu W, Zhou H Front Neurosci. 2024; 18:1349409.
PMID: 38332860 PMC: 10850240. DOI: 10.3389/fnins.2024.1349409.
TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells.
Leon Kropf V, Albany C, Zoccarato A, Green H, Yang Y, Brewer A PLoS One. 2024; 19(1):e0294187.
PMID: 38227585 PMC: 10790995. DOI: 10.1371/journal.pone.0294187.
Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia.
Xie J, Wang Y, Ye C, Li X, Lin L Int J Mol Sci. 2024; 25(1).
PMID: 38203806 PMC: 10779130. DOI: 10.3390/ijms25010636.