Molecular functions of the TLE tetramerization domain in Wnt target gene repression

Chodaparambil, J.V.; Pate, Kira T.; Hepler, Margretta R D; Tsai, Becky Pinjou; Muthurajan, Uma M.; Luger, Karolin; Waterman, Marian L.; Weis, William I.

doi:10.1002/embj.201387188

Cited by 82 publications

(125 citation statements)

References 76 publications

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“…3A; Pereira et al 2006;Tam et al 2008), and when Wnt signaling is activated or TCF3 is absent, core pluripotency factors are up-regulated (Cole et al 2008;Yi et al 2011). When combined with the recent findings of Chodaparambil et al (2014) and the findings delineated for the hair follicle above (Merrill et al 2001;Nguyen et al 2006Nguyen et al , 2009Greco et al 2009;Hsu et al 2014;Lien et al 2014), these findings suggest that binding of b-catenin to TCF3 alters the TCF3-bound repressive chromatin state, in turn activating target genes (Fig. 3B).…”

Section: How Receiving Stem Cells Perceive External Wnt Cuessupporting

confidence: 53%

“…Recent in vitro structural analyses further show that the TLE tetramer functions in chromatin repression through binding to K20 methylated histone H4 tails, which in turn more readily form repressive complexes with TCF3 and TCF4 than with TCF1 and LEF1 (Chodaparambil et al 2014). These findings agree well with recent in vivo ChIP and Illumina deep sequencing (ChIP-seq) and RNA sequencing (RNA-seq) on purified quiescent hair follicle stem cells (HFSCs), which show that TCF3, TCF4, and TLEs bind to common chromatin sites in the absence of Wnt signaling (Lien et al 2014).…”

Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

“…These TCF3/TCF4/TLE-bound genes include chromatin-repressed genes that must be derepressed by canonical Wnt signaling in order to activate hair follicle fate specification (Lien et al 2014). Although it was initially surmised that nuclear b-catenin directly binds LEF/TCF and displaces Groucho/TLE repressors (Daniels and Weis 2005), derepression may not necessarily involve a competitive mechanism (Chodaparambil et al 2014).…”

Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

“…The C-terminal domain of b-catenin includes potent transcriptional transactivation elements that recruit coactivators TBP and CBP/p300. (D) The diagram depicts a model for the Groucho/ TLE proteins (Chodaparambil et al 2014). Most of them share a conserved structural organization, which consists of a glutamine-rich (Q) domain followed by a glycine/proline-rich (GP) domain, CcN domain, serine/proline-rich (SP) domain, and WD repeat domain.…”

Section: How Receiving Stem Cells Perceive External Wnt Cuesmentioning

confidence: 99%

“…Recently, it was shown that TCF3 and TCF4 can bind to the N-terminal region of TLE1, while HDACs are thought to be recruited by TLEs through their GP domain. TCF1 and LEF1 appear to have weaker binding to TLEs, which may account for their more typical behavior as coactivators rather than repressors for Wnt signaling (Chodaparambil et al 2014). Other than TCFs, Groucho/TLEs also interact with other transcriptional factors (e.g., HES1) through their C-terminal region (Grbavec et al 1998).…”

Section: How Receiving Stem Cells Perceive External Wnt Cuesmentioning

confidence: 99%

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Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

2014

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In mammals, Wnt/b-catenin signaling features prominently in stem cells and cancers, but how and for what purposes have been matters of much debate. In this review, we summarize our current knowledge of Wnt/b-catenin signaling and its downstream transcriptional regulators in normal and malignant stem cells. We centered this review largely on three types of stem cells-embryonic stem cells, hair follicle stem cells, and intestinal epithelial stem cells-in which the roles of Wnt/b-catenin have been extensively studied. Using these models, we unravel how many controversial issues surrounding Wnt signaling have been resolved by dissecting the diversity of its downstream circuitry and effectors, often leading to opposite outcomes of Wnt/b-catenin-mediated regulation and differences rooted in stage-and context-dependent effects.

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Section: How Receiving Stem Cells Perceive External Wnt Cuessupporting

confidence: 53%

Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

Section: How Receiving Stem Cells Perceive External Wnt Cuesmentioning

confidence: 99%

Section: How Receiving Stem Cells Perceive External Wnt Cuesmentioning

confidence: 99%

See 3 more Smart Citations

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

2014

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The Wnt Transcriptional Switch: TLE Removal or Inactivation?

et al. 2017

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Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway.

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RUNX1‐dependent mechanisms in biological control and dysregulation in cancer

Hong

Fritz

Gordon

et al. 2018

Journal Cellular Physiology

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The RUNX1 transcription factor has recently been shown to be obligatory for normal development. RUNX1 controls the expression of genes essential for proper development in many cell lineages and tissues including blood, bone, cartilage, hair follicles, and mammary glands. Compromised RUNX1 regulation is associated with many cancers. In this review, we highlight evidence for RUNX1 control in both invertebrate and mammalian development and recent novel findings of perturbed RUNX1 control in breast cancer that has implications for other solid tumors. As RUNX1 is essential for definitive hematopoiesis, RUNX1 mutations in hematopoietic lineage cells have been implicated in the etiology of several leukemias. Studies of solid tumors have revealed a context‐dependent function for RUNX1 either as an oncogene or a tumor suppressor. These RUNX1 functions have been reported for breast, prostate, lung, and skin cancers that are related to cancer subtypes and different stages of tumor development. Growing evidence suggests that RUNX1 suppresses aggressiveness in most breast cancer subtypes particularly in the early stage of tumorigenesis. Several studies have identified RUNX1 suppression of the breast cancer epithelial‐to‐mesenchymal transition. Most recently, RUNX1 repression of cancer stem cells and tumorsphere formation was reported for breast cancer. It is anticipated that these new discoveries of the context‐dependent diversity of RUNX1 functions will lead to innovative therapeutic strategies for the intervention of cancer and other abnormalities of normal tissues.

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Molecular functions of the TLE tetramerization domain in Wnt target gene repression

Cited by 82 publications

References 76 publications

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

RUNX1‐dependent mechanisms in biological control and dysregulation in cancer

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