Analysis of the mouse embryonic stem cell regulatory networks obtained by ChIP-chip and ChIP-PET

Mathur, Divya; Danford, Timothy; Boyer, Laurie A.; Young, Richard A.; Gifford, David K.; Jaenisch, Rudolf

doi:10.1186/gb-2008-9-8-r126

Cited by 54 publications

(52 citation statements)

References 32 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, the regulatory core circuit that controls pluripotency in embryonic stem cells comprises the TFs Oct4, Sox2, Nanog, Klf4, etc. (62)(63)(64)(65) and circuit models comprising few of these TFs qualitatively predict cell fate behavior well. (59,61,66) The idea that a cell type-specific gene expression profile may be a high-dimensional attractor state, as first proposed by Kauffman, (18) has now found experimental support.…”

Section: Problems and Paradigms S Huangmentioning

confidence: 93%

Reprogramming cell fates: reconciling rarity with robustness

2009

View full text Add to dashboard Cite

The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor states that emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust.

show abstract

Section: Problems and Paradigms S Huangmentioning

confidence: 93%

Reprogramming cell fates: reconciling rarity with robustness

2009

View full text Add to dashboard Cite

show abstract

“…ChIP-seq and ChIP-chip location data analysis: factors to consider Comparisons between multiple, apparently similar ChIP experiments can produce a weaker than expected overlap, raising concerns about the reliability of the results that have been obtained (Mathur et al, 2008). The outcomes of ChIP analyses depend heavily on optimised experimental conditions.…”

Section: Global Localisation Of Pluripotency Regulators To Chromatinmentioning

confidence: 99%

The transcriptional foundation of pluripotency

2009

View full text Add to dashboard Cite

A fundamental goal in biology is to understand the molecular basis of cell identity. Pluripotent embryonic stem (ES) cell identity is governed by a set of transcription factors centred on the triumvirate of Oct4, Sox2 and Nanog. These proteins often bind to closely localised genomic sites. Recent studies have identified additional transcriptional modulators that bind to chromatin near sites occupied by Oct4, Sox2 and Nanog. This suggests that the combinatorial control of gene transcription might be fundamental to the ES cell state. Here we discuss how these observations advance our understanding of the transcription factor network that controls pluripotent identity and highlight unresolved issues that arise from these studies.

show abstract

“…Transcriptional regulation is at the heart of the events leading to development, differentiation, and tissue maintenance: not surprisingly, a selected cohort of transcription factors (TFs) are key to ES stemness, by promoting their regulated growth and preventing differentiation. Among these, SOX2, OCT4, KLF4, SALL4, MYC, and NANOG are also involved in the process of reprogramming of differentiated cells to become ES, or ES-like induced pluripotent stem (iPS) cells; genome-wide analysis has established a network of coregulation among these TFs in ESCs [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

The Short Isoform of NF‐YA Belongs to the Embryonic Stem Cell Transcription Factor Circuitry

et al. 2012

View full text Add to dashboard Cite

Totipotency of embryonic stem cells (ESCs) is controlled at the transcriptional level by a handful of transcription factors (TFs) that promote stemness and prevent differentiation. One of the most enriched DNA elements in promoters and enhancers of genes specifically active in ESCs is the CCAAT box, which is recognized by NF-Y, a trimer with histone-like subunits-NF-YB/NF-YC-and the sequence-specific NF-YA. We show that the levels of the short NF-YA isoform-NF-YAs-is high in mouse ESCs (mESCs) and drops after differentiation; a dominant negative mutant affects expression of important stem cells genes, directly and indirectly. Protein transfections of TAT-NF-YAs stimulate growth and compensate for withdrawal of leukemia inhibitory factor (LIF) in cell cultures. Bioinformatic analysis identifies NF-Y sites as highly enriched in genomic loci of stem TFs in ESCs. Specifically, 30%-50% of NANOG peaks have NF-Y sites and indeed NF-Y-binding is required for NANOG association to DNA. These data indicate that NF-Y belongs to the restricted circle of TFs that govern mESCs, and, specifically, that NF-YAs is the active isoform in these cells.

show abstract

Analysis of the mouse embryonic stem cell regulatory networks obtained by ChIP-chip and ChIP-PET

Cited by 54 publications

References 32 publications

Reprogramming cell fates: reconciling rarity with robustness

Reprogramming cell fates: reconciling rarity with robustness

The transcriptional foundation of pluripotency

The Short Isoform of NF‐YA Belongs to the Embryonic Stem Cell Transcription Factor Circuitry

Contact Info

Product

Resources

About