Table 1.

Differentially expressed genes between HDID-1 and HS/Npt mice

Gene symbol	Gene name	Fold change (HDID vs HS/Npt controls)	Description
Tomm22	Translocase of outer mitochondrial membrane 22	2.27–2.71	The encoded protein is an integral membrane protein of the mitochondrial outer membrane. It forms a complex with several other proteins to import cytosolic preproteins into the mitochondrion
Usp29	Ubiquitin specific peptidase 29	1.52–2.14	The encoded protein is a protease that cleaves ubiquitin from proteins and other molecules. Ubiquitination is involved in protein degradation and trafficking
Hmgn2	High mobility group nucleosomal binding domain 2	1.53–1.83	The encoded protein binds nucleosomal DNA and is associated with transcriptionally active chromatin. Along with a similar protein, HMGN1, the encoded protein may help maintain an open chromatin configuration around transcribable genes. The protein has also been found to have antimicrobial activity against bacteria, viruses, and fungi
Pnmal1	Paraneoplastic Ma antigen family-like 1	1.20–1.39	An important paralog of this gene is Zinc Finger, CCHC Domain Containing 12 (ZCCHC12), which codes for a transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway
Vsnl1	Visinin-like 1	1.23–1.49	A member of the visinin/recoverin subfamily of neuronal calcium sensor proteins. The encoded protein associates with membranes in a calcium-dependent manner and modulates intracellular signaling pathways of the central nervous system by directly or indirectly regulating the activity of adenylyl cyclase
Atf4	Activating transcription factor 4	1.17–1.55	Encodes a transcription factor that belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP response element binding proteins (CREBs) and CREB-like proteins. It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to endoplasmic reticulum (ER) stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed: 26086088)
Arhgap35	Rho GTPase activating protein 35	− 1.45 to − 1.85	The encoded protein inhibits glucocorticoid receptor transcription
Trappc13	Trafficking protein particle complex 13	− 1.29 to − 1.45	May play a role in vesicular transport from ER to Golgi

Differential expression analysis was conducted within each brain region using empirical Bayes moderated t statistics in the Bioconductor limma package version 3.24.15 in R to compare male, ethanol-naïve HDID-1 with HS/Npt mice (N = 11-12 mice/genotype). Eight genes were differentially expressed between genotypes across all seven brain regions after correction for multiple tests. Based on the literature, four of the genes (Atf4, Hmgn2, Vsnl1, and Usp29) were alcohol-related