TY - JOUR
T1 - Kinetoplastid-specific histone variant functions are conserved in Leishmania major
AU - Anderson, Britta A.
AU - Wong, Iris L.K.
AU - Baugh, Loren
AU - Ramasamy, Gowthaman
AU - Myler, Peter J.
AU - Beverley, Stephen M.
N1 - Funding Information:
We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, for the use of the Siteman Flow Cytometry Core, which provided the single-cell sorting service. The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant #P30 CA91842. This work was funded by the National Institutes of Health (R0129646 to SMB and ILKW, T32 GM007067 to BAA) and the Washington University Berg-Morse and Schlesinger Graduate Fellowships to BAA. We thank Andrew Haydock and members of our laboratories for discussions.Supplementary data
PY - 2013
Y1 - 2013
N2 - Regions of transcription initiation and termination in kinetoplastid protists lack known eukaryotic promoter and terminator elements, although epigenetic marks such as histone variants and the modified DNA base J have been localized to these regions in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major. Phenotypes of base J mutants vary significantly across trypanosomatids, implying divergence in the epigenetic networks governing transcription during evolution. Here, we demonstrate that the histone variants H2A.Z and H2B.V are essential in L. major using a powerful quantitative plasmid segregation-based test. In contrast, H3.V is not essential for viability or normal growth in Leishmania. Steady-state transcript levels and the efficiency of transcription termination at convergent strand switch regions (SSRs) in H3V-null parasites were comparable to WT parasites. Our genetic tests show a conservation of histone variant phenotypes between L. major and T. brucei, unlike the diversity of phenotypes associated with genetic manipulation of the DNA base J modification.
AB - Regions of transcription initiation and termination in kinetoplastid protists lack known eukaryotic promoter and terminator elements, although epigenetic marks such as histone variants and the modified DNA base J have been localized to these regions in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major. Phenotypes of base J mutants vary significantly across trypanosomatids, implying divergence in the epigenetic networks governing transcription during evolution. Here, we demonstrate that the histone variants H2A.Z and H2B.V are essential in L. major using a powerful quantitative plasmid segregation-based test. In contrast, H3.V is not essential for viability or normal growth in Leishmania. Steady-state transcript levels and the efficiency of transcription termination at convergent strand switch regions (SSRs) in H3V-null parasites were comparable to WT parasites. Our genetic tests show a conservation of histone variant phenotypes between L. major and T. brucei, unlike the diversity of phenotypes associated with genetic manipulation of the DNA base J modification.
KW - Chromatin
KW - Epigenetics
KW - Genetics
KW - Histone variants
KW - Transcriptional read-through
KW - Trypanosomatid protozoa
UR - http://www.scopus.com/inward/record.url?scp=84886732148&partnerID=8YFLogxK
U2 - 10.1016/j.molbiopara.2013.09.005
DO - 10.1016/j.molbiopara.2013.09.005
M3 - Article
C2 - 24080031
AN - SCOPUS:84886732148
SN - 0166-6851
VL - 191
SP - 53
EP - 57
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 2
ER -