H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

被引:11
作者
Connacher, Jessica [1 ]
Josling, Gabrielle A. [2 ,3 ]
Orchard, Lindsey M. [2 ,3 ]
Reader, Janette [1 ]
Llinas, Manuel [2 ,3 ,4 ]
Birkholtz, Lyn-Marie [1 ]
机构
[1] Univ Pretoria, Inst Sustainable Malaria Control, Dept Biochem Genet & Microbiol, Private Bag x20, ZA-0028 Hatfield, Herts, South Africa
[2] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
[3] Penn State Univ, Huck Ctr Malaria Res, University Pk, PA 16802 USA
[4] Penn State Univ, Dept Chem, University Pk, PA 16802 USA
基金
新加坡国家研究基金会;
关键词
Histone; Malaria; Plasmodium; Gametocyte; Epigenetics; Histone post-translational modifications; Histone demethylation; MALARIA PARASITE; HISTONE H3; LYSINE; 36; EPIGENETIC REGULATION; ANTIGENIC VARIATION; SEXUAL DEVELOPMENT; READ ALIGNMENT; TRANSCRIPTION; TRANSMISSION; REVEALS;
D O I
10.1186/s13072-021-00393-9
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background The Plasmodium sexual gametocyte stages are the only transmissible form of the malaria parasite and are thus responsible for the continued transmission of the disease. Gametocytes undergo extensive functional and morphological changes from commitment to maturity, directed by an equally extensive control program. However, the processes that drive the differentiation and development of the gametocyte post-commitment, remain largely unexplored. A previous study reported enrichment of H3K36 di- and tri-methylated (H3K36me2&3) histones in early-stage gametocytes. Using chromatin immunoprecipitation followed by high-throughput sequencing, we identify a stage-specific association between these repressive histone modifications and transcriptional reprogramming that define a stage II gametocyte transition point. Results Here, we show that H3K36me2 and H3K36me3 from stage II gametocytes are associated with repression of genes involved in asexual proliferation and sexual commitment, indicating that H3K36me2&3-mediated repression of such genes is essential to the transition from early gametocyte differentiation to intermediate development. Importantly, we show that the gene encoding the transcription factor AP2-G as commitment master regulator is enriched with H3K36me2&3 and actively repressed in stage II gametocytes, providing the first evidence of ap2-g gene repression in post-commitment gametocytes. Lastly, we associate the enhanced potency of the pan-selective Jumonji inhibitor JIB-04 in gametocytes with the inhibition of histone demethylation including H3K36me2&3 and a disruption of normal transcriptional programs. Conclusions Taken together, our results provide the first description of an association between global gene expression reprogramming and histone post-translational modifications during P. falciparum early sexual development. The stage II gametocyte-specific abundance of H3K36me2&3 manifests predominantly as an independent regulatory mechanism targeted towards genes that are repressed post-commitment. H3K36me2&3-associated repression of genes is therefore involved in key transcriptional shifts that accompany the transition from early gametocyte differentiation to intermediate development.
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页数:15
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共 106 条
[51]   Fast and accurate long-read alignment with Burrows-Wheeler transform [J].
Li, Heng ;
Durbin, Richard .
BIOINFORMATICS, 2010, 26 (05) :589-595
[52]   Fast and accurate short read alignment with Burrows-Wheeler transform [J].
Li, Heng ;
Durbin, Richard .
BIOINFORMATICS, 2009, 25 (14) :1754-1760
[53]   Cross-talk between the H3K36me3 and H4K16ac histone epigenetic marks in DNA double-strand break repair [J].
Li, Lin ;
Wang, Yinsheng .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (28) :11951-11959
[54]   The transcription factor OsSUF4 interacts with SDG725 in promoting H3K36me3 establishment [J].
Liu, Bing ;
Liu, Yuhao ;
Wang, Baihui ;
Luo, Qiang ;
Shi, Jinlei ;
Gan, Jianhua ;
Shen, Wen-Hui ;
Yu, Yu ;
Dong, Aiwu .
NATURE COMMUNICATIONS, 2019, 10 (1)
[55]   Plasmodium gene regulation: far more to factor in [J].
Llinas, Manuel ;
Deitsch, Kirk W. ;
Voss, Till S. .
TRENDS IN PARASITOLOGY, 2008, 24 (12) :551-556
[56]   Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum [J].
Llora-Batlle, Oriol ;
Michel-Todo, Lucas ;
Witmer, Kathrin ;
Toda, Haruka ;
Fernandez-Becerra, Carmen ;
Baum, Jake ;
Cortes, Alfred .
SCIENCE ADVANCES, 2020, 6 (24)
[57]   5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites [J].
Lopez-Rubio, Jose Juan ;
Gontijo, Alisson M. ;
Nunes, Marta C. ;
Issar, Neha ;
Rivas, Rosaura Hernandez ;
Scherf, Artur .
MOLECULAR MICROBIOLOGY, 2007, 66 (06) :1296-1305
[58]   Genome-wide Analysis of Heterochromatin Associates Clonally Variant Gene Regulation with Perinuclear Repressive Centers in Malaria Parasites [J].
Lopez-Rubio, Jose-Juan ;
Mancio-Silva, Liliana ;
Scherf, Artur .
CELL HOST & MICROBE, 2009, 5 (02) :179-190
[59]   Disruption of the Plasmodium falciparum Life Cycle through Transcriptional Reprogramming by Inhibitors of Jumonji Demethylases [J].
Matthews, Krista A. ;
Senagbe, Kossi M. ;
Notzel, Christopher ;
Gonzalez, Christopher A. ;
Tong, Xinran ;
Rijo-Ferreira, Filipa ;
Natarajan, Bhana, V ;
Miguel-Blanco, Celia ;
Jose Lafuente-Monasterio, Maria ;
Garcia, Benjamin A. ;
Kafsack, Bjorn Fc ;
Martinez, Elisabeth D. .
ACS INFECTIOUS DISEASES, 2020, 6 (05) :1058-1075
[60]   Application of dual reading domains as novel reagents in chromatin biology reveals a new H3K9me3 and H3K36me2/3 bivalent chromatin state [J].
Mauser, Rebekka ;
Kungulovski, Goran ;
Keup, Corinna ;
Reinhardt, Richard ;
Jeltsch, Albert .
EPIGENETICS & CHROMATIN, 2017, 10