A Microglial Regulatory Program Linked to Neuropsychiatric Disorders
- 1University of Utah
Abstract
Hoxb8 is a transcription factor required for the normal function of a specialized microglial population. Loss of Hoxb8 causes compulsive overgrooming and anxiety-like behaviors in mice, with greater severity in females after sexual maturity. However, the Hoxb8-dependent transcriptional program in microglia remains poorly understood. Here, we integrated Hoxb8 chromatin occupancy, transcriptional responses, and chromatin contacts to classify genes by their spatial relationship to Hoxb8 binding. Hoxb8 occupied thousands of genomic regions, but only a subset of associated genes responded transcriptionally. Locally associated, Hoxb8-activated genes were linked to immune signaling and hormone responsiveness, whereas locally associated, Hoxb8-suppressed genes were linked to cell-cycle and genome-maintenance processes. Distally associated genes contributed to neuronal and intercellular communication and were enriched for genes associated with obsessive-compulsive disorder and anxiety. These findings reveal a functionally organized Hoxb8-dependent transcriptional program and identify potential connections between Hoxb8 activity in microglia, hormone responsiveness, intercellular communication, and neuropsychiatric disease risk.
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BibTeX
@misc{traenkner2026microglial,
title = {{A Microglial Regulatory Program Linked to Neuropsychiatric Disorders}},
author = {D. Traenkner and A. P. Johnson and M. E. Williams and A. Rothenfluh},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.747643},
url = {https://www.biorxiv.org/content/10.64898/2026.08.27.747643v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Microglial Regulatory Program Linked to Neuropsychiatric Disorders
AU - D. Traenkner
AU - A. P. Johnson
AU - M. E. Williams
AU - A. Rothenfluh
PY - 2026
DA - 2026/08/27
PB - bioRxiv
DO - 10.64898/2026.08.27.747643
UR - https://www.biorxiv.org/content/10.64898/2026.08.27.747643v1
AB - Hoxb8 is a transcription factor required for the normal function of a specialized microglial population. Loss of Hoxb8 causes compulsive overgrooming and anxiety-like behaviors in mice, with greater severity in females after sexual maturity. However, the Hoxb8-dependent transcriptional program in microglia remains poorly understood. Here, we integrated Hoxb8 chromatin occupancy, transcriptional responses, and chromatin contacts to classify genes by their spatial relationship to Hoxb8 binding. Hoxb8 occupied thousands of genomic regions, but only a subset of associated genes responded transcriptionally. Locally associated, Hoxb8-activated genes were linked to immune signaling and hormone responsiveness, whereas locally associated, Hoxb8-suppressed genes were linked to cell-cycle and genome-maintenance processes. Distally associated genes contributed to neuronal and intercellular communication and were enriched for genes associated with obsessive-compulsive disorder and anxiety. These findings reveal a functionally organized Hoxb8-dependent transcriptional program and identify potential connections between Hoxb8 activity in microglia, hormone responsiveness, intercellular communication, and neuropsychiatric disease risk.
ER -