Pioneering, chromatin remodeling, and epigenetic constraint in early T-cell gene regulation by SPI1 (PU.1)

Genome Research
Jonas UngerbäckEllen V Rothenberg

Abstract

SPI1 (also known as PU.1) is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T-cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU.1, and many PU.1 sites lose accessibility when PU.1 is later down-regulated. Pioneering activity of PU.1 was tested in this developmentally dynamic context by quantitating the relationships between PU.1 occupancy and site quality and accessibility as PU.1 levels naturally declined in pro-T-cell development and by using stage-specific gain- and loss-of-function perturbations to relate binding to effects on target genes. PU.1 could bind closed genomic sites, but rapidly opened many of them, despite the absence of its frequent collaborator, CEBPA. RUNX motifs and RUNX1 binding were often linked to PU.1 at open sites, but highly expressed PU.1 could bind its sites without RUNX1. The dynamic properties of PU.1 engagements implied that PU.1 binding affinity and concentration determine its occupancy choices, but with quantitative trade-offs for occupancy between site sequence quality and stage-dependent site accessibility in chromatin. At nonpromoter sites, PU.1 binding criteria were more...Continue Reading

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Citations

Oct 28, 2019·The Journal of Experimental Medicine·Hiroyuki HosokawaEllen V Rothenberg
Aug 6, 2020·EMBO Molecular Medicine·Büşra Erarslan-UysalAndreas E Kulozik
Aug 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Audrey AstoriRajesh Somasundaram
May 8, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Ellen V Rothenberg
Sep 13, 2020·Nature Reviews. Immunology·Hiroyuki Hosokawa, Ellen V Rothenberg
Sep 5, 2019·Genes & Development·Ellen V Rothenberg
Dec 14, 2018·Frontiers in Immunology·Peng Li, Warren J Leonard
Jan 11, 2020·Frontiers in Immunology·Cristiana F PiresCarlos-Filipe Pereira
Aug 7, 2020·The Journal of Cell Biology·Maile Romero-WolfHiroyuki Hosokawa
Jan 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Boyoung ShinEllen V Rothenberg
Feb 25, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hiroyuki HosokawaMaria Koizumi
Jun 29, 2021·The Journal of Experimental Medicine·Hiroyuki HosokawaEllen V Rothenberg
Jul 10, 2021·Scientific Reports·Muhammad Munir IqbalDavid Martino

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