Abstract
First described in 1991, Yin Yang 1 (YY1) is a transcription factor that is ubiquitously expressed throughout mammalian cells. It regulates both transcriptional activation and repression, in a seemingly context-dependent manner. YY1 has a well-established role in the development of the central nervous system, where it is involved in neurogenesis and maintenance of homeostasis in the developing brain. In neurodevelopmental and neurodegenerative disease, the crucial role of YY1 in cellular processes in the central nervous system is further underscored. In this mini-review, we discuss the various mechanisms leading to the transcriptional activating and repressing roles of YY1, including its role as a traditional transcription factor, its interactions with cofactors and chromatin modifiers, the role of YY1 in the non-coding genome and 3D chromatin organization and the possible implications of the phase-separation mechanism on YY1 function. We provide examples on how these processes can be involved in normal development and how alterations can lead to various diseases.
Highlights
Yin Yang 1 (YY1) is a transcription factor (TF) that was first described in 1991 by three independent groups, who all named the protein differently based on the molecular mechanisms they associated it with
YY1 appeared to instigate DNA loop formation and neural progenitor cells (NPCs)-specific promoter-enhancer interactions (Beagan et al, 2017). These YY1mediated DNA loop formations occur within CTCF-CTCF DNA loops (Beagan et al, 2017). These findings introduce a new identity of YY1 as a structural protein in addition to its role as a traditional TF, providing an even broader understanding of the multitude of cellular mechanisms that employ the ubiquitously expressed YY1 protein to regulate transcription
As YY1-regulated genes seemed to be mainly implicated in metabolic pathways and protein translation, influencing the cell cycle machinery indirectly in NPCs and neural crest (NC) (Varum et al, 2019; Zurkirchen et al, 2019), Zurkirchen and colleagues hypothesized that a decreasing dependency on YY1 during cortical development is due to a decreased biosynthetic demand and decreased proliferation rate of cells at later stages of corticogenesis, making these cells less vulnerable to defects in these pathways
Summary
Yin Yang 1 (YY1) is a transcription factor (TF) that was first described in 1991 by three independent groups, who all named the protein differently based on the molecular mechanisms they associated it with. YY1 is able to bind promoter sequences and recruit polymerase by interacting with general TFs. Overlapping DNA binding sites of YY1 and transcriptional activators provide another explanation for YY1-mediated repression. YY1 does not seem essential for 3D chromatin organization, as the majority of its binding sites are close to transcription start sites (TSSs) and only a minority is located distal from regulated genes (Gabriele et al, 2017; Varum et al, 2019; Zurkirchen et al, 2019).
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