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Transcriptional control of microglia phenotypes in health and disease
Inge R. Holtman, … , Dylan Skola, Christopher K. Glass
Inge R. Holtman, … , Dylan Skola, Christopher K. Glass
Published July 31, 2017
Citation Information: J Clin Invest. 2017;127(9):3220-3229. https://doi.org/10.1172/JCI90604.
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Review Series

Transcriptional control of microglia phenotypes in health and disease

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Abstract

Microglia are the main resident macrophage population of the CNS and perform numerous functions required for CNS development, homeostasis, immunity, and repair. Many lines of evidence also indicate that dysregulation of microglia contributes to the pathogenesis of neurodegenerative and behavioral diseases. These observations provide a compelling argument to more clearly define the mechanisms that control microglia identity and function in health and disease. In this Review, we present a conceptual framework for how different classes of transcription factors interact to select and activate regulatory elements that control microglia development and their responses to internal and external signals. We then describe functions of specific transcription factors in normal and pathological contexts and conclude with a consideration of open questions to be addressed in the future.

Authors

Inge R. Holtman, Dylan Skola, Christopher K. Glass

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Figure 2

Different classes of transcription factors interact and regulate cellular identity.

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Different classes of transcription factors interact and regulate cellula...
The top of the figure illustrates the initial steps of enhancer selection in closed chromatin consisting of regularly positioned nucleosomes. Green and blue shading represents closely spaced binding sites for LDTFs. Below, collaborative interactions between LDTFs generate primed enhancers, characterized by a nucleosome-free region and monomethylated H3K4 (H3K4me1). At the bottom of the figure, active SDTFs localize to primed enhancers, resulting in recruitment of coactivators and RNA polymerase II and generation of enhancer RNAs (eRNAs).

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