Abstract
The Prdm (PRDI-BF1-RIZ1 homologous) family is involved in cell differentiation, and several Prdms have been reported to methylate histone H3 by intrinsic or extrinsic pathways. Here, we report that Prdm12 recruits G9a to methylate histone H3 on lysine 9 through its zinc finger domains. Because of the expression of Prdm12 in the developmental nervous system, we investigated the role of Prdm12 on P19 embryonic carcinoma cells as a model system for neurogenesis. In P19 cells, Prdm12 is induced by Retinoic acid (RA). Overproduction of Prdm12 in P19 cells impairs cell proliferation and increases the G1 population accompanied by the upregulation of p27. In contrast, the knockdown of Prdm12 increases the number of cells in a suspension culture of RA-induced neural differentiation. Both the PR domain and zinc finger domains are required for the anti-proliferative activity of Prdm12. While the data in this study is based on in vitro models, the results suggest that Prdm12 is induced by the RA signaling in vivo, and may regulate neural differentiation during animal development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle
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Cell Differentiation / genetics
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Cell Line, Tumor
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
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Embryonal Carcinoma Stem Cells / metabolism*
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HEK293 Cells
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Histone-Lysine N-Methyltransferase / metabolism
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Histones / metabolism
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Humans
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Methylation
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Mice
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nervous System / cytology
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Nervous System / embryology
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Nervous System / metabolism
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Neurogenesis
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RNA Interference
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RNA, Small Interfering
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Signal Transduction
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tretinoin / metabolism*
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Zinc Fingers
Substances
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Carrier Proteins
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Histones
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Nerve Tissue Proteins
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Prdm12 protein, human
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Prdm12 protein, mouse
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RNA, Small Interfering
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Transcription Factors
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Cyclin-Dependent Kinase Inhibitor p27
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Tretinoin
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Histone-Lysine N-Methyltransferase