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: #

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...

-modifying TrxG proteins # chromatin-remodeling TrxG proteins # DNA-binding TrxG proteins, plus other TrxG proteins not categorized in the first three classes.

Discovery

The founding member of TrxG proteins, trithorax (trx), was discovered ~1978 by

Philip Ingham Philip William Ingham FRS, FMedSci, Hon. FRCP (born 19 March 1955 Liverpool) is a British geneticist, currently the Toh Kian Chui Distinguished Professor at the Lee Kong Chian School of Medicine, a partnership between Nanyang Technological Un ...

as part of his doctoral thesis while a graduate student in the laboratory of J.R.S. Whittle at the

University of Sussex , mottoeng = Be Still and Know , established = , type = Public research university , endowment = £14.4 million (2020) , budget = £319.6 million (2019–20) , chancellor = Sanjeev Bhaskar , vice_chancellor = Sasha Roseneil , ...

. Histone-lysine ''N''-methyltransferase 2A is the human homolog of trx. The table contains names of Drosophila TrxG members. Homologs in other species may have different names.

Function

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 Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence ge ...

, TrxG proteins are most commonly linked to

gene activation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...

. The trithorax complex activates gene transcription by inducing trimethylation of lysine 4 of histone H3 (

H3K4me3 H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates tri-methylation at the 4th lysine residue of the histone H3 protein and is often involved in the regulation of gene expression. The name denotes the addi ...

) at specific sites in chromatin recognized by the complex. Ash1 domain is involved in H3K36 methylation. Trithorax complex also interacts with

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(CREB binding protein) which is an acetyltransferase to acetylate H3K27. This gene activation is reinforced by acetylation of

histone H4 Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on ...

. The actions of TrxG proteins are often described as 'antagonistic' of PcG proteins function. Aside from gene regulation, evidence suggests TrxG proteins are also involved in other processes including apoptosis, cancer, and stress responses.

Role in development

During development, TrxG proteins maintain activation of required genes, particularly the

Hox genes Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the co ...

, after maternal factors are depleted. This is accomplished by preserving the epigenetic marks, specifically H3K4me3, established by maternally-supplied factors. TrxG proteins are also implicated in

X-chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...

, which occurs during early embryogenesis. 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.

References

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External links

The Polycomb and Trithorax page of the Cavalli lab
This page contains useful information on Polycomb and trithorax proteins, in the form of an introduction, links to published reviews, list of Polycomb and trithorax proteins, illustrative power point slides and a link to a genome browser showing the genome-wide distribution of these proteins in Drosophila melanogaster.

DNA-binding proteins Molecular genetics Drosophila melanogaster genes

Discovery

Function

Role in development

See also

References

External links