Smarcc1/Baf155 Couples Self-Renewal Gene Repression with Changes in Chromatin Structure in Mouse Embryonic Stem Cells

Schaniel, Christoph; Ang, Yen Sin; Ratnakumar, Kajan; Cormier, Catherine; James, Taneisha; Bernstein, Emily; Lemischka, Ihor R.; Paddison, Patrick J.

doi:10.1002/stem.223

Cited by 141 publications

(148 citation statements)

References 55 publications

(110 reference statements)

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“…To test whether Nanog autorepression exists in ESCs, we performed both Nanog overexpression and knockdown studies in NG4 transgenic ESCs expressing the enhanced green fluorescent protein (GFP) reporter gene under the control of the endogenous Nanog promoter (P Nanog ) (Fig. 1A, Left) (15). First, we introduced a doxycycline (Dox)-inducible Nanog transgene bearing a Flag-biotin dual tag (FLbio) and established stable clones by puromycin selection (Fig.…”

Section: Resultsmentioning

confidence: 99%

Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

Fidalgo

Faiola

Pereira

et al. 2012

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

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The homeodomain transcription factor Nanog plays an important role in embryonic stem cell (ESC) self-renewal and is essential for acquiring ground-state pluripotency during reprogramming. Understanding how Nanog is transcriptionally regulated is important for further dissecting mechanisms of ESC pluripotency and somatic cell reprogramming. Here, we report that Nanog is subjected to a negative autoregulatory mechanism, i.e., autorepression, in ESCs, and that such autorepression requires the coordinated action of the Nanog partner and transcriptional repressor Zfp281. Mechanistically, Zfp281 recruits the NuRD repressor complex onto the Nanog locus and maintains its integrity to mediate Nanog autorepression and, functionally, Zfp281-mediated Nanog autorepression presents a roadblock to efficient somatic cell reprogramming. Our results identify a unique transcriptional regulatory mode of Nanog gene expression and shed light into the mechanistic understanding of Nanog function in pluripotency and reprogramming.

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Section: Resultsmentioning

confidence: 99%

Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

Fidalgo

Faiola

Pereira

et al. 2012

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

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110

132

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“…Patrick Paddison and colleagues used a library of shRNAs enriched for gene targets involved in chromatin regulation, signal transduction, and transcription (Schaniel et al 2009). They transfected shRNAs into mESCs harboring a Nanog-GFP reporter, and cells were treated with retinoic acid, which induces differentiation and reduces Nanog-GFP activity.…”

Section: Potential Tcf-independent Mechanismsmentioning

confidence: 99%

Wnt Pathway Regulation of Embryonic Stem Cell Self-Renewal

Merrill

2012

Cold Spring Harbor Perspectives in Biology

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“…In embryonic stem cells, the esBAF complex has been defined and shown to differ in its subunit composition from differentiated derivatives (17). The important role of BAF components such as Smarca4/Brg1 and Smarcc1/Baf155 in pluripotency has been shown by their role in direct repression of key pluripotency-regulating genes during differentiation of embryonic stem cells (18,19).…”

mentioning

confidence: 99%

DNA and Chromatin Modification Networks Distinguish Stem Cell Pluripotent Ground States

Song¹,

Saha²,

Gokulrangan³

et al. 2012

Molecular & Cellular Proteomics

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Pluripotent stem cells are capable of differentiating into all cell types of the body and therefore hold tremendous promise for regenerative medicine. Despite their widespread use in laboratories across the world, a detailed understanding of the molecular mechanisms that regulate the pluripotent state is currently lacking. Mouse embryonic (mESC) and epiblast (mEpiSC) stem cells are two closely related classes of pluripotent stem cells, derived from distinct embryonic tissues. Although both mESC and mEpiSC are pluripotent, these cell types show important differences in their properties suggesting distinct pluripotent ground states. To understand the molecular basis of pluripotency, we analyzed the nuclear proteomes of mESCs and mEpiSCs to identify protein networks that regulate their respective pluripotent states. Our study used label-free LC-MS/MS to identify and quantify 1597 proteins in embryonic and epiblast stem cell nuclei. Immunoblotting of a selected protein subset was used to confirm that key components of chromatin regulatory networks are differentially expressed in mESCs and mEpiSCs. Specifically, we identify differential expression of DNA methylation, ATP-dependent chromatin remodeling and nucleosome remodeling networks in mESC and mEpiSC nuclei. This study is the first comparative study of protein networks in cells representing the two distinct, pluripotent states, and points to the importance of DNA and chromatin modification processes in regulating pluripotency. In addition, by integrating our data with existing pluripotency networks, we provide detailed maps of protein networks that regulate pluripotency that will further both the fundamental understanding of pluripotency as well as efforts to reliably control the differentiation of these cells into functional cell fates. Molecular & Cellular Proteomics

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Smarcc1/Baf155 Couples Self-Renewal Gene Repression with Changes in Chromatin Structure in Mouse Embryonic Stem Cells

Cited by 141 publications

References 55 publications

Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

Wnt Pathway Regulation of Embryonic Stem Cell Self-Renewal

DNA and Chromatin Modification Networks Distinguish Stem Cell Pluripotent Ground States

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