Different Behavioral Experiences Produce Distinctive Parallel Changes in, and Correlate With, Frontal Cortex and Hippocampal Global Post-translational Histone Levels

Abstract

While it is clear that behavioral experience modulates epigenetic profiles, it is less evident how the nature of that experience influences outcomes and whether epigenetic/genetic “biomarkers” could be extracted to classify different types of behavioral experience. To begin to address this question, male and female mice were subjected to either a Fixed Interval (FI) schedule of food reward, or a single episode of forced swim followed by restraint stress, or no explicit behavioral experience after which global expression levels of two activating (H3K9ac and H3K4me3) and two repressive (H3K9me2 and H3k27me3) post-translational histone modifications (PTHMs), were measured in hippocampus (HIPP) and frontal cortex (FC). The specific nature of the behavioral experience differentiated profiles of PTHMs in a sex- and brain region-dependent manner, with all 4 PTHMs changing in parallel in response to different behavioral experiences. These different behavioral experiences also modified the pattern of correlations of PTHMs both within and across FC and HIPP. Unexpectedly, highly robust correlations were found between global PTHM levels and behavioral performances, suggesting that global PTHMs may provide a higher-order pattern recognition function. Further efforts are needed to determine the generality of such findings and what characteristics of behavioral experience are critical for modulating PTHM responses.

The histone H3 lysine 9 methyltransferase G9a/GLP complex activity is required for long-term consolidation of spatial memory in mice

“…During recent years, growing body of evidence has emerged to suggest sex differences in regionally specific recruitment of histone PTMs and histones modifying enzymes involved in regulating transcription of genes important for learning and/or memory (Keiser & Wood, 2019). Interestingly, a recent study revealed that different behavioral experiences produced sex-specific differences of global histone H3K9 acetylation and methylation patterns, both within and across the dorsal HPC and frontal cortex (Sobolewski, Singh, Schneider, & Cory-Slechta, 2018). Furthermore, higher levels of both HDAC activity and/or DNA methyltransferase 1 content have been reported in the HPC and cortices of females compared to males, indicators of increased transcriptional activity repression (Elsner, Cechinel, de Meireles, Bertoldi, & Siqueira, 2018;Tsai, Grant, & Rissman, 2009).…”

The Person’s Care Requires a Sex and Gender Approach

“… Data from [ 42 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ] and cited literature. F = female; M = male; UGT = UDP-glucuronosyl-transferase; SULT = sulfotransferase; SLC = solute carrier family; MRP = multidrug resistance protein; Oatp = organic anion-transporting polypeptide.…”