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

ABSTRACT: Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. Although 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 analyzed three conditional knockout mouse lines, in which the essential PRC2 subunits embryonic ectoderm development (EED), suppressor of zeste 12 homolog (Suz12), and enhancer of zeste homologs 1 and 2 (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.

SUBMITTER: Dauber KL

PROVIDER: S-EPMC4958613 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Dauber Katherine L KL Perdigoto Carolina N CN Valdes Victor J VJ Santoriello Francis J FJ Cohen Idan I Ezhkova Elena E

The Journal of investigative dermatology 20160316 8

Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. Although 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 analyzed three conditional knockout mouse lines, in whic ...[more]

PMID: 26994968

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Project description:BACKGROUND: Epigenetic regulation is necessary for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. One such complex, the Polycomb Repressive Complex 2 (PRC2), is critical to many developmental processes in plants including the regulation of major developmental transitions. In addition, PRC2 restricts the expression domain of various transcription factor families in Arabidopsis, including the class I KNOX genes and several of the ABCE class MADS box genes. While the functions of these transcription factors are known to be deeply conserved, whether or not their regulation by PRC2 is similarly conserved remains an open question. RESULTS: Here we use virus-induced gene silencing (VIGS) to characterize the function of the PRC2 complex in lateral organ development of Aquilegia x coerulea 'Origami', a member of the lower eudicot order Ranunculales. Leaves with PRC2 down-regulation displayed a range of phenotypes including ruffled or curled laminae, additional lobing, and an increased frequency of higher order branching. Sepals and petals were also affected, being narrowed, distorted, or, in the case of the sepals, exhibiting partial homeotic transformation. Many of the petal limbs also had a particularly intense yellow coloration due to an accumulation of carotenoid pigments. We show that the A. x coerulea floral MADS box genes AGAMOUS1 (AqAG1), APETALA3-3 (AqAP3-3) and SEPALLATA3 (AqSEP3) are up-regulated in many tissues, while expression of the class I KNOX genes and several candidate genes involved in carotenoid production or degradation are largely unaffected. CONCLUSIONS: PRC2 targeting of several floral MADS box genes may be conserved in dicots, but other known targets do not appear to be. In the case of the type I KNOX genes, this may reflect a regulatory shift associated with the evolution of compound leaves.

Dataset Information

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

Publications

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

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