Trithorax-group proteins (TrxG) are a heterogeneous collection of proteins whose main action is to maintain

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

. 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 and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...

-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 (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 University, Singapore and Im ...

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

University of Sussex The University of Sussex is a public university, public research university, research university located in Falmer, East Sussex, England. It lies mostly within the city boundaries of Brighton and Hove. Its large campus site is surrounded by the ...

. 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 (genetics), transcription or Translation (biology), translation and is often used in res ...

, 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 wide ...

. 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 addit ...

) at specific sites in chromatin recognized by the complex. Ash1 domain is involved in H3K36 methylation. Trithorax complex also interacts with CBP (CREB binding protein) which is an acetyltransferase to acetylate H3K27. This gene activation is reinforced by

acetylation : In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply ''acetates''. Deacetylation is the opposite react ...

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

. 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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, 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 c ...

, after maternal factors are depleted. This is accomplished by preserving the

epigenetic In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

marks, specifically H3K4me3, established by maternally-supplied factors. TrxG proteins are also implicated in X-chromosome inactivation, which occurs during early

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

. 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

{{Reflist, colwidth=35em

External links

The Polycomb and Trithorax page of the Cavalli lab at IGH (Institut de Génétique Humaine)
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