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Published on: January 26, 2018
The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C. elegans
Laurel B Bender1, Ru Cao, Yi Zhang
1Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Abstract:
The C. elegans proteins MES-2 and MES-6, orthologs of the Polycomb group (PcG) chromatin repressors E(Z) and ESC, exist in a complex with their novel partner MES-3. The MES system participates in silencing the X chromosomes in the hermaphrodite germline. Loss of maternal MES function leads to germline degeneration and sterility. We report here that the MES complex is responsible for di- and trimethylation of histone H3 Lys27 (H3-K27) in the adult germline and in early embryos and that MES-dependent H3-K27 marks are concentrated on the X's. Another H3-K27 HMT functions in adult somatic cells, oocytes, and the PGCs of embryos. In PGCs, the MES complex may specifically convert dimethyl to trimethyl H3-K27. The HMT activity of the MES complex appears to be dependent on the SET domain of MES-2. MES-2 thus joins its orthologs Drosophila E(Z) and human EZH2 among SET domain proteins known to function as HMTs (reviewed in ). Methylation of histones is important for long-term epigenetic regulation of chromatin and plays a key role in diverse processes such as X inactivation and oncogenesis. Our results contribute to understanding the composition and roles of E(Z)/MES-2 complexes across species.
Insights
The MES complex in C. elegans methylates histone H3 Lys27 (H3-K27) on X chromosomes, crucial for germline development and silencing. This epigenetic regulation is vital for preventing sterility and germline degeneration.
Area of Science:
- Epigenetics
- Chromatin Biology
- Developmental Biology
Background:
- Polycomb group (PcG) proteins regulate gene expression through chromatin modification.
- The C. elegans MES complex (MES-2, MES-3, MES-6) is involved in X chromosome silencing in the germline.
- Loss of maternal MES function results in sterility and germline degeneration.
Purpose of the Study:
- To investigate the biochemical activity of the MES complex.
- To determine the role of the MES complex in histone methylation.
- To elucidate the function of MES-dependent histone modifications in C. elegans development.
Main Methods:
- Biochemical assays to assess histone methyltransferase (HMT) activity.
- Immunohistochemistry to detect H3-K27 methylation marks.
- Analysis of MES complex components and their interactions.
Main Results:
- The MES complex catalyzes di- and trimethylation of histone H3 Lys27 (H3-K27).
- MES-dependent H3-K27 methylation is concentrated on X chromosomes in the germline and early embryos.
- MES-2's SET domain is essential for its HMT activity, similar to Drosophila E(Z) and human EZH2.
Conclusions:
- The MES complex functions as a histone H3 Lys27 methyltransferase, essential for X chromosome silencing and germline integrity in C. elegans.
- MES-dependent H3-K27 methylation is a key epigenetic mechanism for developmental processes.
- This study expands the understanding of PcG complex function and histone methylation across species.
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