Trithorax-group proteins

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:

  1. histone-modifying TrxG proteins
  2. chromatin-remodeling TrxG proteins
  3. DNA-binding TrxG proteins,

plus other TrxG proteins not categorized in the first three classes.[1]

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.[2] Histone-lysine N-methyltransferase 2A is the human homolog of trx.[2]

Members of Trithorax Group Proteins:
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

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, 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]

Role in development

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] As of 2011 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]

See also

References
  1. Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G (February 2007). "Genome regulation by polycomb and trithorax proteins". Cell. 128 (4): 735–45. doi:10.1016/j.cell.2007.02.009. PMID 17320510.
  2. Ingham PW (1998). "trithorax and the regulation of homeotic gene expression in Drosophila: a historical perspective". Int. J. Dev. Biol. 42 (3): 423–9. PMID 9654027.
  3. Geisler, Sarah J.; Paro, Renato (2015-09-01). "Trithorax and Polycomb group-dependent regulation: a tale of opposing activities". Development. 142 (17): 2876–2887. doi:10.1242/dev.120030. ISSN 0950-1991. PMID 26329598.
  4. Grimaud C, Nègre N, Cavalli G (2006). "From genetics to epigenetics: the tale of Polycomb group and trithorax group genes". Chromosome Res. 14 (4): 363–75. doi:10.1007/s10577-006-1069-y. PMID 16821133. S2CID 19504262.
  5. Tyagi S, Herr W (October 2009). "E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases". EMBO J. 28 (20): 3185–95. doi:10.1038/emboj.2009.258. PMC 2771094. PMID 19763085.
  6. Siebold AP, Banerjee R, Tie F, Kiss DL, Moskowitz J, Harte PJ (January 2010). "Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance". Proc. Natl. Acad. Sci. U.S.A. 107 (1): 169–74. doi:10.1073/pnas.0907739107. PMC 2806727. PMID 20018689.
  7. Bagchi A, Papazoglu C, Wu Y, Capurso D, Brodt M, Francis D, Bredel M, Vogel H, Mills AA (February 2007). "CHD5 is a tumor suppressor at human 1p36". Cell. 128 (3): 459–75. doi:10.1016/j.cell.2006.11.052. PMID 17289567.
  8. Brock HW, Fisher CL (March 2005). "Maintenance of gene expression patterns". Dev. Dyn. 232 (3): 633–55. doi:10.1002/dvdy.20298. PMID 15704101.
  9. Soshnikova N (August 2011). "Dynamics of Polycomb and Trithorax activities during development". Birth Defects Research Part A: Clinical and Molecular Teratology. 91 (8): 781–7. doi:10.1002/bdra.20774. PMID 21290568.
  10. Pullirsch D, Härtel R, Kishimoto H, Leeb M, Steiner G, Wutz A (March 2010). "The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation". Development. 137 (6): 935–43. doi:10.1242/dev.035956. PMC 2834461. PMID 20150277.
  11. Schuettengruber B, Martinez AM, Iovino N, Cavalli G (December 2011). "Trithorax group proteins: switching genes on and keeping them active". Nat. Rev. Mol. Cell Biol. 12 (12): 799–814. doi:10.1038/nrm3230. hdl:21.11116/0000-0006-0774-0. PMID 22108599. S2CID 19992445.
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