Extrasynaptic α5GABAA receptors and their role in nociception and pathological pain

Franco-Enzástiga, Úrzula; Luz-Cuellar, Yarim Elideth De la; Hernández-Reyes, Luis Eduardo; Raya-Tafolla, Guadalupe; Torres-López, Jorge Elías; Murbartián, Janet; Granados‐Soto, Vinicio; Delgado‐Lezama, Rodolfo

doi:10.1016/b978-0-12-820589-1.00012-9

Cited by 1 publication

(1 citation statement)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of these genes were associated with DARs on autosomes, like GABRA5. Previous studies have shown that the alpha-5 GABAergic receptor (encoded by the Gabra5 gene in mice) is more highly expressed in the female rodent DRG where it plays an important role in pain signaling and where it is epigenetically regulated in a sex-specific fashion (72,73). We also found a higher accessibility in autosomal BDNF-AS in females, a lncRNA that suppresses BDNF expression.…”

Section: Discussionsupporting

confidence: 63%

Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes

Franco-Enzástiga,

Inturi,

Natarajan

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand regulation of gene expression in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible chromatin technology followed by sequencing (ATAC-seq). We detected a total of 3005 differentially accessible chromatin regions (DARs) between sexes using bulk ATAC-seq. DARs in female hDRG mapped mainly to the X chromosome. In males, DARs were found in autosomal genes. We also found differential transcription factor binding motifs within DARs. EGR1/3 and SP1/4 were abundant in females, and JUN, FOS and other AP-1 family members in males. With the aim of dissecting the open chromatin profile in hDRG neurons, we used spatial ATAC-seq. Consistent with our bulk ATAC-seq data, most of the DARs in female hDRG were located in X chromosome genes. Neuron cluster showed higher chromatin accessibility in GABAergic, glutamatergic, and interferon-related genes in females, and in Ca2+-signaling-related genes in males. Sex differences in open chromatin transcription factor binding sites in neuron-proximal barcodes were consistent with the bulk data, having EGR1 transcription factor activity in females and AP-1 family members in males. Accordingly, we showed higher expression of EGR1 in female hDRG compared to male with in-situ hybridization. Our findings point to epigenomic sex differences in the hDRG that likely underlie divergent transcriptional responses that determine mechanistic sex differences in pain.

show abstract

Section: Discussionsupporting

confidence: 63%