Dataset Information

Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes.

ABSTRACT: Studies on human lysine-specific demethylase 2A (KDM2A) by others have recently begun. To date, the demethylase activity has been known to reduce expression of genes and eventually inhibit proliferation of cells. However, while attempting to improve proliferation of hES-cell-derived Nod keratinocytes, which grow poorly and have a short life span, we found that high expression of the KDM2A gene improves the poor proliferation of the cells. Of the four isomer cDNAs that we prepared from alternatively spliced KDM2A transcripts, only one stimulates the proliferation. This (KDM2A-N782) encodes the 782AA protein containing the JmjC, CXXC, and Ring domains, but not the F-box and AMN1 domains, unlike KDM2A, which has been studied by other groups. Our results not only show that differently spliced transcripts from a gene result in totally opposite outcomes, but also present critical evidence of the complicated activities of KDM2A, which contains all of the five domains.

SUBMITTER: Iuchi S

PROVIDER: S-EPMC3386085 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes.

Iuchi Shiro S Green Howard H

Proceedings of the National Academy of Sciences of the United States of America 20120525 24

Studies on human lysine-specific demethylase 2A (KDM2A) by others have recently begun. To date, the demethylase activity has been known to reduce expression of genes and eventually inhibit proliferation of cells. However, while attempting to improve proliferation of hES-cell-derived Nod keratinocytes, which grow poorly and have a short life span, we found that high expression of the KDM2A gene improves the poor proliferation of the cells. Of the four isomer cDNAs that we prepared from alternativ ...[more]

PMID: 22635273

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Project description:The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of Kdm2a, the zona pellucida 3-Cre (Zp3-Cre)/LoxP system was used to generate an oocyte Kdm2a conditional knockout (Zp3-Cre; Kdm2aflox/flox, termed Kdm2a cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult Kdm2a cKO female mice mating with wildtype males than that of the control (Kdm2aflox/flox) group. To analyze the potential causes, the ovaries of Kdm2a cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between Kdm2a cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout Kdm2a, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of Kdm2a cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of Kdm2a, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in Kdm2a cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout Kdm2a gene led to female subfertility, suggesting the crucial role of Kdm2a in epigenetic modification and follicular and oocyte development.

Dataset Information

Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes.

Publications

Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes.

Similar Datasets

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