Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein.
Synthesis of the modified thymine base beta-D-glucosyl-hydroxymethyluracil, or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream-form-specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. The mechanism of developmental and telomeric-specific regulation of J synthesis is unknown. We have previously identified a J binding protein (JBP1) involved in propagating J synthesis. We have now identified a homolog of JBP1, JBP2, containing a domain related to the SWI2/SNF2 family of chromatin remodeling proteins that is upregulated in bloodstream form cells and interacts with nuclear chromatin. We show that expression of JBP2 in procyclic form cells leads to de novo J synthesis within telomeric regions of the chromosome and that this activity is inhibited after mutagenesis of conserved residues critical for SWI2/SNF2 function. We propose a model in which chromatin remodeling by JBP2 regulates the initial sites of J synthesis within bloodstream form trypanosome DNA, with further propagation and maintenance of J by JBP1.
DiPaolo
Courtney
C
Global Infectious Diseases Program, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
Kieft
Rudo
R
Cross
Mike
M
Sabatini
Robert
R
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016054:DNA, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan; D005960:Glucosides / Q000737:chemistry; D006031:Glycosylation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
D016054:DNA, Protozoan; D004268:DNA-Binding Proteins; D005960:Glucosides; C402790:J-specific DNA-binding protein, protozoa; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C084880:5-((glucopyranosyloxy)methyl)uracil; D014498:Uracil; D000251:Adenosine Triphosphatases