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LDB1 establishes multi-enhancer networks to regulate gene expression.

Mol Cell

January 2025

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:

How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements.

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Treatments which inhibit or inactivate Cdk1/cyclin B in metaphase-arrested mammalian cells and budding yeast are described. These treatments induce the cells to exit mitosis and return to interphase, though without chromosome segregation or cytokinesis, and they provide the basis for a method to identify enzymes or other proteins which act "downstream" from Cdk1 inactivation and to elucidate the roles of those proteins in mitotic exit. In this method, inactivation of Cdk1 is combined with inhibition or inactivation of a protein of interest and the effects are observed.

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How specific enhancer-promoter pairing is established is still mostly unclear. Besides the CTCF/cohesin machinery, only a few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Here, we show via acute degradation experiments that LDB1 directly and broadly promotes enhancer-promoter loops.

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Few 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, the formation of YY1-dependent enhancer-promoter loops does not involve stalling of cohesin-mediated loop extrusion.

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Cell cycle is known to be regulated by the underlying gene network. Chromosomes, which serve as the scaffold for gene expressions, undergo significant structural reorganizations during mitosis. Understanding the mechanism of the cell cycle from the chromosome structural perspective remains a grand challenge.

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