Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity

Léveillé, Nicolas; Vermeulen, Louis

doi:10.21037/sci.2016.06.03

Cited by 4 publications

(2 citation statements)

References 38 publications

(30 reference statements)

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“…It seems likely therefore, that a significant contribution to MITF's residency time is made by protein-protein interactions. Given the role of CTCF in determining and stabilizing chromatin topology though binding to boundary elements 68,70 , and the role of PRC1 in 3D chromatin organization and control of cell identity [71][72][73][74] , it is plausible that MITF's tight association with nuclear structures 30 and long residency times reflects a similar role in establishing chromatin conformations that determine the melanocyte lineage. This would be consistent with observations made on the residence time of the neuronal lineage-determining factor Ascl1 using in vivo competition assays 75 .…”

Section: Discussionmentioning

confidence: 99%

Acetylation reprograms MITF target selectivity

Goding

Louphrasitthiphol

Loffreda

et al. 2022

Preprint

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The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long (>100s) residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.

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Section: Discussionmentioning

confidence: 99%

Acetylation reprograms MITF target selectivity

Goding

Louphrasitthiphol

Loffreda

et al. 2022

Preprint

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“…Moreover, CBX7 also marks a specific population of adult intestinal stem cells (ISCs) located at the base of intestinal crypts 39 . The CBX7 + ISCs are normally quiescent, whereas a second group of CBX7 low ISCs undergoes continuous proliferation 40 . This finding correlates with our observation that CBX7 is highly expressed in olfactory HBCs, yet GBCs expresses lower levels of CBX7.…”

Section: Discussionmentioning

confidence: 99%

Potential role of CBX7 in regulating pluripotency of adult human pluripotent-like olfactory stem cells in stroke model

Fan

Lee

et al. 2018

Cell Death Dis

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The adult olfactory mucosa, a highly regenerative tissue with unique life-long neurogenesis ability, is thought to harbor a naïve yet tightly controlled stem cell population. It will provide unique benefits in various stem cell-based therapies, such as stroke treatment. Here, we identified a subpopulation of adult pluripotent-like olfactory stem cells (APOSCs), which were modulated by an epigenetic repressor of CBX7. APOSCs form a floating sphere, express pluripotency markers Nanog, Oct-4, Sox-2, and SSEA-4 and show alkaline phosphatase activity. In addition, APOSCs display self-renewal and a pluripotent potential to differentiate into all three germ layers. Moreover, APOSCs coexpress pluripotency markers with CBX7. Within their natural niche, APOSCs from CBX7+/+ mice responded promptly to either spontaneous or injury-induced tissue regeneration. However, APOSCs from CBX7−/− mice manifested an impaired self-renewal and differentiation potential. Similarly, in vitro-cultivated CBX7−/− APOSCs underwent premature senescence, whereas CBX7+/+ APOSCs still actively divided, indicating that CBX7 is required for the self-renewal of APOSCs. Intracerebral implantation of APOSCs improved the stroke-mediated neurological dysfunction in rodents. These findings indicate that CBX7 plays a critical role in the regenerative properties of APOSCs and indicate the safety and feasibility of implantation of autologous APOSCs in stroke treatment.

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