2008
DOI: 10.1101/gad.1673508
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Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

Abstract: The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may dynamically regulate gene expression, but this potential role in mammalian tissue homeostasis remains uncharacterized. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. During calcium-induced differentiation, H3K27me3 was erased at these promoters in concert with loss of PcG protein occupancy and increased binding by the H3K27me3 demethylas… Show more

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Cited by 248 publications
(295 citation statements)
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“…As a primary example, the H3K27me3 histone lysine demethylase JMJD3 functions to mediate stem cell differentiation potential. In undifferentiated human keratinocytes, a form of unipotent adult stem cell, JMJD3 is required to remove repressive H3K27me3 marks at pro-differentiation genes (Sen et al, 2008). Consistently, overexpression of JMJD3 drives premature keratinocyte differentiation (Sen et al, 2008).…”
Section: Histone Demethylases As Regulators Of Reversible Chromatin Smentioning
confidence: 95%
See 1 more Smart Citation
“…As a primary example, the H3K27me3 histone lysine demethylase JMJD3 functions to mediate stem cell differentiation potential. In undifferentiated human keratinocytes, a form of unipotent adult stem cell, JMJD3 is required to remove repressive H3K27me3 marks at pro-differentiation genes (Sen et al, 2008). Consistently, overexpression of JMJD3 drives premature keratinocyte differentiation (Sen et al, 2008).…”
Section: Histone Demethylases As Regulators Of Reversible Chromatin Smentioning
confidence: 95%
“…In undifferentiated human keratinocytes, a form of unipotent adult stem cell, JMJD3 is required to remove repressive H3K27me3 marks at pro-differentiation genes (Sen et al, 2008). Consistently, overexpression of JMJD3 drives premature keratinocyte differentiation (Sen et al, 2008). Similarly, in the developing nervous system of mice, JMJD3 promotes differentiation upon induction of retinoic acid signaling, and its suppression is required for the maintenance of an uncommitted stem cell state (Jepsen et al, 2007).…”
Section: Histone Demethylases As Regulators Of Reversible Chromatin Smentioning
confidence: 97%
“…Lysis with a modified RIPA buffer (1% NP40/Igepal, 0.5% Sodium Deoxycholate, 0.1% SDS, 100 uM EDTA in PBS), nuclei were isolated and overnight pulldown was performed with an antibody to MITF (Sigma HPA003259), H3K27ac (Abcam ab4729), H3K4me1 (Abcam ab8895), or Rabbit IgG control (Abcam ab37415). Staph A cells were used for pulldown and washes were performed as described previously (Sen et al 2008). Isolated DNA was subject to qPCR with primers in Supplemental Table 6.…”
Section: Chromatin Immunoprecipitationmentioning
confidence: 99%
“…Cells were trypsinized, washed, and cross-linked as described previously (Sen et al 2008). Lysis with a modified RIPA buffer (1% NP40/Igepal, 0.5% Sodium Deoxycholate, 0.1% SDS, 100 uM EDTA in PBS), nuclei were isolated and overnight pulldown was performed with an antibody to MITF (Sigma HPA003259), H3K27ac (Abcam ab4729), H3K4me1 (Abcam ab8895), or Rabbit IgG control (Abcam ab37415).…”
Section: Chromatin Immunoprecipitationmentioning
confidence: 99%
“…Double conditional knockout mice for HDAC1/2 have thin, smooth skin and failure for limb-digit separation and eyelid fusion (LeBoeuf et al 2010). Small interfering RNA-mediated deletion of JMJD3, an H3K27me3 demethylase in organotypic human epidermal cultures, prevented epidermal differentiation, whereas conversely, JMJD3 overexpression led to premature differentiation (Sen et al 2008). Whereas conditional deletion in the epidermis of the polycomb complex protein Ezh2 alone leads to rather mild phenotype (Ezhkova et al 2009), conditional deletion of both EZH1/2 differentially affects HF and IFE.…”
Section: Fine-tuning Of Epidermal Differentiation and Homeostasis By mentioning
confidence: 99%