Epigenetic Regulation of Epidermal Differentiation

Perdigoto, Carolina N.; Valdés, Victor J.; Bardot, Evan S.; Ezhkova, Elena

doi:10.1101/cshperspect.a015263

Cited by 47 publications

(68 citation statements)

References 123 publications

(144 reference statements)

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“…Understanding how this complex functions in stem cells in vivo is of paramount importance, as a wide variety of human genomic studies have revealed the importance of the Polycomb proteins for different human diseases (Perdigoto et al , 2014b; Sauvageau and Sauvageau, 2010). …”

Section: Discussionmentioning

confidence: 99%

“…Polycomb repressive complex (PRC) 2 is a major chromatin repressor (Schwartz and Pirrotta, 2013) that regulates tissue development and fate control, and is implicated in a number of diseases, including cancer (Margueron and Reinberg, 2011; Perdigoto et al , 2014b; Sauvageau and Sauvageau, 2010; Schwartz and Pirrotta, 2008; Surface et al , 2010). PRC2 consists of the core subunits EED, Suz12, and the histone methyltransferases Ezh1 or Ezh2, which catalyse the tri-methylation of lysine 27 of histone H3 (H3K27me3), resulting in gene silencing by chromatin compaction (Margueron et al , 2008; Schwartz and Pirrotta, 2013; Simon and Kingston, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development

Dauber

Perdigoto

Valdés

et al. 2016

Journal of Investigative Dermatology

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Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. While there have been numerous studies on PRC2 function in somatic tissue development and stem cell control, these have focused on the loss of a single PRC2 subunit. Recent studies, however, have shown that PRC2 subunits may function independently of the PRC2 complex. To investigate the function of PRC2 in the control of skin development, we generated and analysed three conditional knockout mouse lines, in which the essential PRC2 subunits EED, Suz12, or Ezh1/2 are conditionally ablated in the embryonic epidermal progenitors that give rise to the epidermis, hair follicles, and Merkel cells. Our studies showed that the observed loss-of-function phenotypes are shared between the three knockouts, indicating that in the skin epithelium, EED, Suz12, and Ezh1/2 function largely as subunits of the PRC2 complex. Interestingly, the absence of PRC2 results in dramatically different phenotypes across the different skin lineages: premature acquisition of a functional epidermal barrier, formation of ectopic Merkel cells, and defective postnatal development of hair follicles. The strikingly different roles of PRC2 in the formation of three lineages exemplify the complex outcomes that the lack of PRC2 can have in a somatic stem cell system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development

Dauber

Perdigoto

Valdés

et al. 2016

Journal of Investigative Dermatology

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“…Cell differentiation is an insightful example of the importance of epigenetic regulation [1]. An example of epigenetic regulation is a fertilized egg that gives rise to an organism that consists of hundreds of different cell types, morphologically and functionally, while preserving genetic information contributed by both parents [2, 3].…”

Section: Introductionbmentioning

confidence: 99%

Chromatin immunoprecipitation for human monocyte derived macrophages

Wooden

Ciborowski²

2014

Methods

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The importance of Chromatin Immunoprecipitation (ChIP) technology has grown exponentially along with an increased interest in epigenetic regulation. The correlation of transcription factors with histone marks is now well established as the center of epigenetic studies; therefore, precise knowledge about histone marks is critical to unravel their molecular function and to understand their role in biological systems. This knowledge constantly accumulates and is provided openly in the expanding hubs of information such as the USCS Genome Browser. Nevertheless, as we gain more knowledge, we realize that the DNA-protein interactions are not driven by a “one size fits all” rule. Also, the diversity of interactions between DNA, histones, and transcriptional regulators is much bigger than previously considered. Besides a detailed protocol of sample preparation for the ChIP assay from primary human monocyte-derived macrophages (MDM)a, we show that differences between various types of cells exist. Furthermore, we can postulate that such variations exist between transformed macrophage-like cell lines and primary macrophages obtained from healthy volunteers. We found that the most efficient fixation time for MDM is 10 minutes. Finally, to perform multiple analytical assays, we showed that even with thorough methodology, the yield of material obtained from primary cells is the major challenge.

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“…Epigenetic regulators exhibit both activating and repressive effects on chromatin in keratinocytes (KCs): histone demethylase Jmjd3, ATP-dependent chromatin remodeler Brg1, and genome organizer Satb1 promote terminal KC differentiation, while DNA methyltransferase DNMT1, histone deacetylases HDAC1/2, and Polycomp components Bmi1 and Ezh1/2 stimulate proliferation of progenitor cells via repression of the genes encoding cell cycle inhibitors, as well as inhibit premature activation of terminal differentiation-associated genes (reviewed in (Eckert et al, 2011;Frye and Benitah, 2012;Botchkarev et al, 2012;Perdigoto et al, 2014).…”

mentioning

confidence: 96%

“…The program of epidermal development and keratinocyte differentiation is governed by coordinated involvement of several transcription factors (p63, AP-1, Klf4, Arnt, and so on), signaling pathways (Wnt, Bmp, Hedgehog, EGF, Notch, FGF, and so on), and epigenetic regulators (DNA/histonemodifying enzymes, Polycomb genes, higher-order and ATP-dependent chromatin remodelers, and non-coding RNAs) that control expression of lineage-specific genes (reviewed in (Frye and Benitah, 2012;Botchkarev et al, 2012;Perdigoto et al, 2014)). …”

mentioning

confidence: 98%