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Here, we identify the key factors that regulate the cellular abundance and activity of these two histone deacetylases. Our results demonstrate that<jats:italic>PfSIR2A<\/jats:italic>and<jats:italic>PfSIR2B<\/jats:italic>are transcriptionally downregulated at the mid\u2010ring stage in response to febrile temperature. We found that the molecular chaperone PfHsp90 acts as a repressor of<jats:italic>PfSIR2A<\/jats:italic>&amp;<jats:italic>B<\/jats:italic>transcription. By virtue of its presence in the<jats:italic>PfSIR2A<\/jats:italic>&amp;<jats:italic>B<\/jats:italic>promoter proximal regions PfHsp90 helps recruiting H3K9me3, conferring heterochromatic state, and thereby leading to the downregulation of<jats:italic>PfSIR2A<\/jats:italic>&amp;<jats:italic>B<\/jats:italic>transcription. Such transcriptional downregulation can be reversed by the addition of 17\u2010(allylamino)\u201017\u2010demethoxygeldanamycin or Radicicol, two potent inhibitors of PfHsp90. The reduced occupancy of PfSir2 at sub\u2010telomeric<jats:italic>var<\/jats:italic>promoters leads to the de\u2010repression of<jats:italic>var<\/jats:italic>genes. Thus, here we uncover how exposure to febrile temperature, a hallmark of malaria, enables the parasites to manipulate the expression of the two prominent epigenetic modifiers PfSir2A and PfSir2B.<\/jats:p>","DOI":"10.1111\/mmi.14692","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T04:24:28Z","timestamp":1612585468000},"page":"1025-1038","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Febrile temperature causes transcriptional downregulation of<i>Plasmodium falciparum<\/i>Sirtuins through Hsp90\u2010dependent epigenetic modification"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-4564","authenticated-orcid":false,"given":"Wahida","family":"Tabassum","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Life Sciences University of Hyderabad Hyderabad 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