Transcriptional and Epigenetic Regulation of Microglia in Health and Disease

Trends Mol Med. 2019 Feb;25(2):96-111. doi: 10.1016/j.molmed.2018.11.004. Epub 2018 Dec 18.

Abstract

Microglia are the resident immune cells that maintain brain homeostasis and contribute to neurodegenerative disorders. Recent studies of microglia at transcriptomic and epigenetic levels revealed specific molecular pathways that regulate microglia development, maturation, and reactive states. The transcription factor PU.1 plays a key role in regulating several microglial functions. Environmental factors such as microbiota, early life stress, and maternal immune activation can dysregulate PU.1 and innate immune response. This review discusses the epigenetic regulation of key transcriptional factors in human and murine microglia, highlighting their networks for shaping the microglial function. PU.1 and other microglia-specific transcriptional factors can be further studied to determine their therapeutic applications in neurologic disorders.

Keywords: PU.1; microglia; microglia transcription; neurodegenerative disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic*
  • Gene Regulatory Networks
  • Humans
  • Microglia / metabolism
  • Microglia / pathology*
  • Nervous System Diseases / genetics
  • Nervous System Diseases / pathology
  • Proto-Oncogene Proteins / genetics*
  • Trans-Activators / genetics*
  • Transcriptional Activation
  • Transcriptome*

Substances

  • Proto-Oncogene Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1