Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells

By E. Ezhkova, H. Pasolli, J. Parker, N. Stokes, I-hsin Su, Gregory J. Hannon, A. Tarakhovsky, Elaine Fuchs. Cell, 2009

628 citations recorded by the source corpus.

SUMMARY Although in vitro studies of embryonic stem cells have identified polycomb repressor complexes (PRCs) as key regulators of differentiation, it remains unclear as to how PRC-mediated mechanisms control fates of multipotent progenitors in developing tissues. Here, we show that an essential PRC component, Ezh2, is expressed in epidermal progenitors but diminishes concomitant with embryonic differentiation and with postnatal decline in proliferative activity. We show that Ezh2 controls proliferative potential of basal progenitors by repressing the Ink4A-Ink4B locus and tempers the developmental rate of differentiation by preventing premature recruitment of AP1 transcriptional activator to the structural genes that are required for epidermal differentiation. Together, our studies reveal that PRCs control epigenetic modifications temporally and spatially in tissue-restricted stem cells. They maintain their proliferative potential and globally repressing undesirable differentiation programs while selectively establishing a specific terminal differentiation program in a stepwise fashion.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a8e52c91abd5ac212b18dd439d2efa2710b857e1

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Citations in the corpus

Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put (2013, background): “Do PcG components remain bound at genomic targets, or does binding need to be re-established after each mitotic transition? Earlier studies using fixed or live-cell imaging reached divergent opinions as to whether fly PcG proteins are substantially retained on mitotic chromatin (Buchenau et al., 199”
Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa (2010, background): “, a modification associated with gene repression in developmen”
Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. (2010, neutral): “Similar observations have been reported for many somatic tissues (Ezhkova et al., 2009; Caretti et al., 2004; Hirabayashi et al., 2009; Zencak et al., 2005).”
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. (2017, neutral): “…several studies demonstrated an essential role for PRC1 and PRC2 in the patterning and homeostasis of the adult mouse intestine, skin, craniofacial structures, and hematopoietic systems (Chiacchiera et al., 2016; Ezhkova et al., 2009; Hidalgo et al., 2012; Minoux et al., 2017; Xie et al., 2014).”
Single-cell dissection of transcriptional heterogeneity in human colon tumors (2011, background): “The OLMF4 + / CA2 high and the LGR5 + / ASCL2 + compartments shared expression of several genes of functional interest in both stem cell and cancer biology, such as genes involved in self-renewal and chromatin remodeling ( EZH2 , BMI1”