TrxG proteins have been defined as factors suppressing the Polycomb phenotypes in Drosophila, indicating the opposing mechanistic function of the gene products. The TrxG protein complexes have diverse molecular functions with catalytic activities generally associated with active transcription. Many TrxG proteins are essential for preserving transcriptional patterns, and thereby cell fate, and the genes encoding TrxG proteins are often found mutated or deregulated in human cancers¹.

The TrxG proteins also segregate into large, multimeric protein complexes. These complexes can be largely divided into two groups: COMPASS/COMPASS-like and SWI/SNF (mammalian homologs called BAF/PBAF).

COMPASS and COMPASS-like complexes

COMPASS and COMPASS-like complexes are SET-domain containing methyltransferases, catalyzing mono-, di- and trimethylation of H3K4. The catalytic core of these complexes consists of WDR5, ASH2, RBBP5, and DPY30 (WARD). Each specific complex incorporates a SET-domain-containing methyltransferase (SET1, MLL1/2, or MLL3/4) as well as numerous additional subunits, yielding distinct chromatin binding patterns and additional catalytic activities to the complexes².

You can find more details on different COMPASS and COMPASS-like complexes in the full guide.

Different COMPASS complexes regulate H3K4 methylation in distinct genomic regions. SET1-COMPASS catalyzes H3K4me3 at the promoters of actively transcribed genes. MLL1/2-COMPASS-like complexes catalyze H3K4me3 at developmentally regulated and bivalent genes also marked by H3K27me3. MLL3/4 COMPASS-like complexes are responsible for the establishment of H3K4me1 at enhancer elements.

SWI/SNF complexes

The SWI/SNF complexes are ATP-dependent chromatin-remodeling complexes mediating nucleosome sliding or eviction associated with active transcription. In mammalian cells, the two SWI/SNF ATPase homologs, SMARCA4/BRG1 or SMARCA2/BRM each interact with about eight additional proteins to form the core complex, shared by both BAF and PBAF. Additional complex-specific subunits provide functional diversity to the complexes; this includes subunits ARID1A/B and DPF1/2/3 for BAF and PBRM1, BRD7, ARID2, and PHF10 for PBAF.

SWI/SNF protein complexes maintain an open chromatin environment through nucleosome remodeling. SWI/SNF (BAF/PBAF) protein complexes are recruited to CGIs at the promoters of transcribed genes, where they contribute to maintaining an open, permissive chromatin environment through ATPase-dependent chromatin remodeling and exclusion of PRCs.

References

1. Alfert, A., Moreno, N., Kerl, K. The BAF complex in development and disease Epigenetics Chromatin 12 (19), (2019)
2. Schuettengruber, B., Bourbon, H. M., Di Croce, L., et al. Genome regulation by polycomb and trithorax: 70 years and counting Cell 171 ,34-57 (2017)