Trithorax-group proteins (TrxG) are a heterogeneous collection of proteins whose main action is to maintain
gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
. They can be categorized into three general classes based on molecular function:
#
histone-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 as part of his doctoral thesis while a graduate student in the laboratory of J.R.S. Whittle at the
University of Sussex.
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
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
-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.
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 organic 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 oppo ...
of
histone H4. 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 grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, cancer, and stress responses.
Role in development
During development, TrxG proteins maintain activation of required genes, particularly the
Hox genes, after maternal factors are depleted.
This is accomplished by preserving the
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
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 an initial stage of development of 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 sperm ...
.
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.
See also
*
HIstome
*
Histone acetyltransferase
*
Histone deacetylases
*
Histone methyltransferase
Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...
*
Histone-Modifying Enzymes
*
Nucleosome
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...
*
PRMT4 pathway
References
{{Reflist, colwidth=35em
External links
The Polycomb and Trithorax page of the Cavalli labThis 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