Interrogating the role of YY1 in chromatin organization and transcription throughout the cell cycle

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Degree type
Doctor of Philosophy (PhD)
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Genomics and Computational Biology
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Biology
Genetics and Genomics
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01/01/2024
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Lam, Jessica
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Abstract

Few DNA-binding transcription factors have been examined for their direct roles in physically connecting enhancers and promoters. Here, acute degradation of Yin Yang 1 (YY1) in erythroid cells revealed its requirement for the maintenance of numerous enhancer-promoter loops, but not compartments or domains. Despite its reported ability to interact with cohesin, formation of YY1-dependent enhancer-promoter loops does not involve stalling of cohesin-mediated loop extrusion. Integrating mitosis-to-G1 phase dynamics, we observed partial retention of YY1 on mitotic chromatin, predominantly at gene promoters, followed by rapid re-binding during mitotic exit, coinciding with enhancer-promoter loop establishment. YY1 degradation during the mitosis-to-G1 phase interval revealed a set of enhancer-promoter loops that requires YY1 for establishment during G1 phase entry, but not for maintenance in interphase, suggesting that cell cycle stage influences YY1’s architectural function. Thus, as revealed here for YY1, chromatin architectural functions of transcription factors can vary in their interplay with CTCF and cohesin and by cell cycle stage.

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Blobel, Gerd, A
Date of degree
2024
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