Histone modifications in Trypanosoma brucei.
Several biological processes in Trypanosoma brucei are affected by chromatin structure, including gene expression, cell cycle regulation, and life-cycle stage differentiation. In Saccharomyces cerevisiae and other organisms, chromatin structure is dependent upon posttranslational modifications of histones, which have been mapped in detail. The tails of the four core histones of T. brucei are highly diverged from those of mammals and yeasts, so sites of potential modification cannot be reliably inferred, and no cross-species antibodies are available to map the modifications. We therefore undertook an extensive survey to identify posttranslational modifications by Edman degradation and mass spectrometry. Edman analysis showed that the N-terminal alanine of H2A, H2B, and H4 could be monomethylated. We found that the histone H4 N-terminus is heavily modified, while, in contrast to other organisms, the histone H2A and H2B N-termini have relatively few modifications. Histone H3 appears to have a number of modifications at the N-terminus, but we were unable to assign many of these to a specific amino acid. Therefore, we focused our efforts on uncovering modification states of H4. We discuss the potential relevance of these modifications.
Mandava
Veena
V
Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY 10021, USA.
Fernandez
Joseph P
JP
Deng
Haiteng
H
Janzen
Christian J
CJ
Hake
Sandra B
SB
Cross
George A M
GA
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D053719:Tandem Mass Spectrometry; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D015800:Protozoan Proteins
Nature. 1981 Jul 16;292(5820):265-7
7254319
Nucleic Acids Res. 1980 Oct 24;8(20):4671-80
6255427
Int J Pept Protein Res. 1989 Aug;34(2):118-23
2807728
J Parasitol. 1989 Dec;75(6):985-9
2614608
Cell. 1995 Nov 17;83(4):555-61
7585958
EMBO J. 2003 Nov 3;22(21):5851-62
14592982
Nature. 1997 Sep 25;389(6649):349-52
9311776
EMBO J. 1997 Dec 15;16(24):7422-31
9405371
Dev Biol. 1999 Mar 15;207(2):322-33
10068466
J Biol Chem. 2004 Dec 17;279(51):53458-64
15456746
J Mol Biol. 2005 Feb 11;346(1):135-46
15663933
Science. 2005 Jul 15;309(5733):436-42
16020728
J Biol Chem. 2005 Nov 18;280(46):38814-22
16166085
Anal Chem. 2005 Dec 15;77(24):7845-51
16351129
Mol Cell Proteomics. 2006 Jan;5(1):194-203
16210244
FEBS Lett. 2006 Apr 17;580(9):2306-10
16580668
Mol Cell. 2006 Aug;23(4):497-507
16916638
Mol Biochem Parasitol. 2006 Dec;150(2):268-77
17010453
Mol Cell. 2000 Dec;6(6):1309-20
11163205
Science. 2001 Sep 28;293(5539):2453-5
11498546
J Biol Chem. 2001 Oct 12;276(41):38261-71
11477078
Curr Opin Cell Biol. 2003 Apr;15(2):172-83
12648673
Nat Rev Mol Cell Biol. 2003 Apr;4(4):276-84
12671650
Nature. 2003 Oct 2;425(6957):475-9
14523437
Trends Genet. 2003 Nov;19(11):629-39
14585615
Proteomics. 2004 Jan;4(1):1-10
14730666
Nature. 2004 Oct 14;431(7010):873-8
15386022
Exp Parasitol. 1974 Apr;35(2):196-208
4206929
Proc Natl Acad Sci U S A. 1977 Mar;74(3):864-8
265581
J Mol Biol. 1987 Oct 5;197(3):471-83
2831370