Trithorax-group proteins (TrxG) are a heterogeneous collection of proteins whose main action is to maintain gene expression. They can be categorized into three general classes based on molecular function:
plus other TrxG proteins not categorized in the first three classes.[1]
The founding member of TrxG proteins, trithorax (trx), was discovered ~1978 by Philip Ingham as part of his doctoral thesis while a graduate student in the laboratory of J.R.S. Whittle at the University of Sussex.[2] Histone-lysine N-methyltransferase 2A is the human homolog of trx.[2]
| Name | Symbol(s) | |
|---|---|---|
| absent, small or homeotic discs 1 | ash1 | |
| absent, small or homeotic discs 2 | ash2 | |
| brahma | brm | |
| Brahma associated protein 55kD | Bap55 | |
| Brahma associated protein 60 kD | Bap60 | |
| dalao | dalao | |
| domino | dom | |
| Enhancer of bithorax | E(bx) | |
| enhancer of yellow 3 | SAYP or e(y)3 | |
| eyelid | eld or osa | |
| female sterile (1) homeotic | fs(1)h | |
| grappa | gpp | |
| Imitation SWI | Iswi | |
| kismet | kis | |
| little imaginal discs | lid | |
| lola like | lolal | |
| modifier of mdg 4 | mod(mdg4), E(var)3-93D, or doom | |
| moira | mor | |
| Nucleosome remodeling factor-38kD | Nurf38 | |
| trithorax | trx | |
| Trithorax like | Trl | |
| Ubiquitously transcribed tetratricopeptide repeat, X chromosome | Utx | |
| verthandi | vtd | |
| zeste | z |
Trithorax-group proteins typically function in large complexes formed with other proteins. The complexes formed by TrxG proteins are divided into two groups: histone-modifying complexes and ATP-dependent chromatin-remodeling complexes. The main function of TrxG proteins, along with polycomb group (PcG) proteins, is regulating gene expression. Whereas PcG proteins are typically associated with gene silencing, TrxG proteins are most commonly linked to gene activation. The trithorax complex activates gene transcription by inducing trimethylation of lysine 4 of histone H3 (H3K4me3) at specific sites in chromatin recognized by the complex.[1] Ash1 domain is involved in H3K36 methylation. Trithorax complex also interacts with CBP (CREB binding protein) which is an acetyltransferase to acetylate H3K27.[3] This gene activation is reinforced by acetylation of histone H4. The actions of TrxG proteins are often described as 'antagonistic' of PcG proteins function.[4] Aside from gene regulation, evidence suggests TrxG proteins are also involved in other processes including apoptosis, cancer, and stress responses.[5] [6] [7]
During development, TrxG proteins maintain activation of required genes, particularly the Hox genes, after maternal factors are depleted.[8] This is accomplished by preserving the epigenetic marks, specifically H3K4me3, established by maternally-supplied factors.[9] TrxG proteins are also implicated in X-chromosome inactivation, which occurs during early embryogenesis.[10] it is unclear whether TrxG activity is required in every cell during the entire development of an organism or only during certain stages in certain cell types.[11]