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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 1

Enhancers and promoters interact to confer cell type–specific expression and response profiles.

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Enhancers and promoters interact to confer cell type–specific expression...
Promoters are primarily occupied by general sequence-specific transcription factors (TFs), but are also important sites of action of lineage-determining TFs (LDTFs) and signal-dependent TFs (SDTFs). Enhancers are primarily selected by LDTFs and are usually the most numerous binding sites for SDTFs. External and internal signals converge on SDTFs to regulate enhancer and promoter function.
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