Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

Seo, Seongjin; Kroll, Kristen L.

doi:10.4161/cc.5.4.2438

Cited by 60 publications

(59 citation statements)

References 74 publications

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“…Expression in the medial wall of the telencephalon suggests an involvement in signaling events patterning the telencephalon. Balanced interactions of Geminin with Cdt1 and transcriptional modulators have been suggested to affect proliferationdifferentiation decisions during neurogenesis (1,17). The identification of Idas as a novel Geminin binding partner expressed in the developing brain, which is implicated in the cell cycle and can compete for Geminin-Cdt1 interactions, suggests a regulatory role for Idas in proliferation-differentiation decisions during neurogenesis.…”

Section: Figure 3 Idas Directly Binds To Geminin In Vitro and Prevenmentioning

confidence: 99%

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Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression

Pefani

Dimaki

Spella

et al. 2011

Journal of Biological Chemistry

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Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.Development and homeostasis of multicellular organisms depends on the generation of the appropriate number of cells through cell proliferation and the acquisition of specialized cell functions through cell differentiation. Geminin has been suggested to regulate proliferation-differentiation decisions through balanced interactions with the DNA replication licensing factor Cdt1 and factors regulating transcription during development (1).

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Section: Figure 3 Idas Directly Binds To Geminin In Vitro and Prevenmentioning

confidence: 99%

“…Geminin has been suggested to regulate proliferation-differentiation decisions through balanced interactions with the DNA replication licensing factor Cdt1 and factors regulating transcription during development (1).…”

mentioning

confidence: 99%

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression

Pefani

Dimaki

Spella

et al. 2011

Journal of Biological Chemistry

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“…Dimitris Karamitros, l Panorea Kotantaki, l Zoi Lygerou, 2 Henrique Veiga-Fernandes, 3,4 Vassilis Pachnis, 5 A number of studies over the past 10 years have shed more light into the function of Geminin at the molecular level and have suggested that Geminin may coordinate proliferation and differentiation decisions through direct interactions with multiple binding partners. [3][4][5] Geminin, a small coiled-coil protein present in metazoa, inhibits licensing of origins for DNA replication through binding and inhibiting Cdtl, a key member of the pre-replicative complex.…”

Section: Life Without Gemininmentioning

confidence: 99%

“…[3][4][5] Geminin, a small coiled-coil protein present in metazoa, inhibits licensing of origins for DNA replication through binding and inhibiting Cdtl, a key member of the pre-replicative complex. [6][7][8] Geminin binding to Cdt1 during the S and G 2 phases of the cell cycle inhibits re-replication of origins that have already fired, thereby ensuring once per cell cycle replication and genome stability.…”

Section: Life Without Gemininmentioning

confidence: 99%

Life without geminin

et al. 2010

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“…Geminin is reported to inhibit the license of DNA replication initiation in the S to G 2 -M phase by binding to the replication license factor Cdt-1 (38). Expression of a geminin mutant lacking the D-box domain and relatively resistant to proteolysis occurring in the G 1 phase was induced in a doxycycline-dependent manner in Runx3-expressing OVA53 cells.…”

Section: Runx3 and Th-pok Antagonize Each Other And Are Reciprocally mentioning

confidence: 96%

Reciprocal Control of G1-Phase Progression Is Required for Th-POK/Runx3–Mediated CD4/8 Thymocyte Cell Fate Decision

Sato

Chiba

Ohno

et al. 2012

The Journal of Immunology

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After receiving a TCR-mediated differentiation signal, CD4 and CD8 double-positive thymocytes diverge into CD4 or CD8 single-positive T cells, for which Th-POK and Runx3 have been identified as pivotal transcription factors, respectively. The cross-antagonistic regulation of Th-POK and Runx3 seems to be essential for CD4/8 thymocyte lineage commitment. However, the process for determining which pivotal factor acts dominantly has not been established. To explore the determining process, we used an in vitro culture system in which CD4 or CD8 single-positive cells are selectively induced from CD4/8 double-positive cells. Surprisingly, we found that control of G1 cell cycle phase progression is critical for the determination. In the CD4 pathway, sustained TCR signal, as well as Th-POK, induces G1-phase extension and represses CD8 expression in a G1 extension-dependent manner. In the CD8 pathway, after receiving a transient TCR signal, the IL-7R signal, as well as Runx3, antagonizes TCR signal-mediated G1 extension and CD8 repression. Importantly, forced G1 extension cancels the functions of Runx3 to repress Th-POK and CD4 and to reactivate CD8. In contrast, it is suggested that forced G1 progression inhibits Th-POK function to repress CD8. Collectively, Th-POK and Runx3 are reciprocally involved in the control of G1-phase progression, on which they exert their functions dependently. These findings may provide novel insight into how CD4/CD8 cell lineages are determined by Th-POK and Runx3.

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Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

Cited by 60 publications

References 74 publications

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression

Life without geminin

Reciprocal Control of G1-Phase Progression Is Required for Th-POK/Runx3–Mediated CD4/8 Thymocyte Cell Fate Decision

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