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.

Current Biology : CB
|September 24, 2004
PubMed

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.

Related Concept Videos

Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Heterochromatin02:38

Heterochromatin

The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Euchromatin01:01

Euchromatin

The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...