SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick<i>Nkx2.5</i>enhancer

Lee, Kyu‐Ho; Evans, Susan; Ruan, Todd Y.; Lassar, Andrew B.

doi:10.1242/dev.01344

Cited by 74 publications

(72 citation statements)

References 55 publications

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“…COS-7 cells were transfected with the indicated expression vehicles. Nuclear extracts from these cells were incubated with radiolabeled oligos carrying a Gli binding site located upstream of the Gli1 promoter (Dai et al, 1999) (lanes 1-5) or a GATA binding site located upstream of the Nkx2.5 promoter (Lee et al, 2004) (lanes 6-10). (C) NIH 3T3 cells were co-transfected with GAL4-firefly luciferase and SV40 renilla luciferase (control) plus expression vehicles encoding the Gal4 DNA-binding domain alone (lanes 1-3) or the Gal4 DNA-binding domain fused to GLI1 (lanes 4-6) or Gli3FL (lanes 7-9) in the absence or presence of GATA4-ZF-VP16 or GATA4-ZF.…”

Section: Gata4 Can Interact With Gli Factorsmentioning

confidence: 99%

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BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

et al. 2014

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The relative timing of SHH and BMP signals controls whether presomitic mesoderm (PSM) cells will adopt either a chondrogenic or lateral plate mesoderm fate. Here we document that SHH-mediated induction of Nkx3.2 maintains the competence of somitic cells to initiate chondrogenesis in response to subsequent BMP signals by repressing BMP-dependent induction of GATA genes. Conversely, administration of BMP signals to PSM or forced expression of GATA family members in chick PSM explants blocks induction of hedgehogdependent gene expression. We demonstrate that GATA factors can interact with Gli factors and can recruit the transcriptional co-factor FOG1 (ZFPM1) to the regulatory region of the mouse Gli1 gene, repressing the induction of Gli1 by SHH by binding to both GATA and Gli binding sites. Knockdown of FOG1 reverses the ability of GATA factors to repress Gli1 expression. Our findings uncover a novel role for GATA transcription factors as repressors of hedgehog signaling, and document that NKX3.2 maintains the ability of sclerotomal cells to express SHH transcriptional targets in the presence of BMP signals by repressing the induction of Gata4/5/6.

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Section: Gata4 Can Interact With Gli Factorsmentioning

confidence: 99%

“…The probes used for Gli-BS and GATA-BS were described previously (Sasaki et al, 1997;Lee et al, 2004).…”

Section: Generation Of Gata4-or Gata5-expressing Sufumentioning

confidence: 99%

BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

et al. 2014

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“…Smad1 protein has also been found to physically interact with HoxC8, Nkx3-2, YY1, ␤-catenin/Lef1 complex, and Gata factors 4, 5, and 6 (Shi et al, 1999;Kim and Lassar, 2003;Benchabane and Wrana, 2003;Brown et al, 2004;Lee et al, 2004;Hu and Rosenblum, 2005).…”

Section: Transcription Factor Partners For Smads In the Regulation Ofmentioning

confidence: 99%

Finding partners: How BMPs select their targets

Blitz

Cho

2009

Developmental Dynamics

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The bone morphogenetic protein (BMP) signaling pathway is a conserved and evolutionarily ancient regulatory module affecting a large variety of cellular behaviors. The evolutionary flexibility in using BMP responses presumably arose by co-option of a canonical BMP signaling cascade to regulate the transcription of diverse batteries of target genes. This begs the question of how seemingly interchangeable BMP signaling components elicit widely different outputs in different cell types, an important issue in the context of understanding how BMP signaling integrates with gene regulatory networks to control development. Because a molecular understanding of how BMP signaling activates different batteries of target genes is an essential prerequisite to comprehending the roles of BMPs in regulating cellular responses, here we review the current knowledge of how BMP-regulated target genes are selected by the signal transduction machinery. We highlight recent studies suggesting the evolutionary conservation of BMP target gene regulation signaling by Schnurri family zinc finger proteins.

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“…Overlapping binding sites for SMAD1 and YY1 have also been identified in the regulatory regions of histone genes, specifically in differentiated cells (33). Furthermore, YY1 and SMAD1 jointly regulate expression of genes during cardiac development (35). Based on these considerations, we suggest that BMP activates XIST expression by promoting YY1-mediated activation of XIST.…”

Section: Discussionmentioning

confidence: 78%

Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression

Sripathy

Leko

Adrianse

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome. Because restoration of MeCP2 expression in a mouse model reverses neurologic deficits in adult animals, reactivation of the wild-type copy of MeCP2 on the inactive X chromosome (Xi) presents a therapeutic opportunity in RS. To identify genes involved in MeCP2 silencing, we screened a library of 60,000 shRNAs using a cell line with a MeCP2 reporter on the Xi and found 30 genes clustered in seven functional groups. More than half encoded proteins with known enzymatic activity, and six were members of the bone morphogenetic protein (BMP)/TGF-β pathway. shRNAs directed against each of these six genes down-regulated X-inactive specific transcript (XIST), a key player in X-chromosome inactivation that encodes an RNA that coats the silent X chromosome, and modulation of regulators of this pathway both in cell culture and in mice demonstrated robust regulation of XIST. Moreover, we show that Rnf12, an X-encoded ubiquitin ligase important for initiation of X-chromosome inactivation and XIST transcription in ES cells, also plays a role in maintenance of the inactive state through regulation of BMP/TGF-β signaling. Our results identify pharmacologically suitable targets for reactivation of MeCP2 on the Xi and a genetic circuitry that maintains XIST expression and X-chromosome inactivation in differentiated cells.XIST | X inactivation | MeCP2 | Rett syndrome | BMP/TGF-β

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SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chickNkx2.5enhancer

Abstract: . Our data suggest that BMP-mediated activation of this regulatory region reflects both the induction of GATA genes by BMP signals, as well as modulation of the transcriptional activity of YY1 by direct interaction of this transcription factor with BMP-activated SMADs.

Cited by 74 publications

References 55 publications

BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

Finding partners: How BMPs select their targets

Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression

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