Interplay between DOT1L and HDAC1 regulates Leishmania donovani infection in human THP-1 cells.

Autor: Kanojia A; Chromatin Remodeling Laboratory, School of Life Sciences, JNU, New Delhi, 110067, India., Roy G; Chromatin Remodeling Laboratory, School of Life Sciences, JNU, New Delhi, 110067, India., Madhubala R; Chromatin Remodeling Laboratory, School of Life Sciences, JNU, New Delhi, 110067, India., Muthuswami R; Chromatin Remodeling Laboratory, School of Life Sciences, JNU, New Delhi, 110067, India. Electronic address: rohini_m@mail.jnu.ac.in.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2024 Oct; Vol. 258, pp. 107352. Date of Electronic Publication: 2024 Aug 04.
DOI: 10.1016/j.actatropica.2024.107352
Abstrakt: Leishmania donovani, a protozoan parasite, causes visceral leishmaniasis. The parasite modifies the global gene expressions of the host genome, facilitating its survival within the host. Thus, the host epigenetic modulators play important roles in host-pathogen interaction and host epigenetic modification in response to infection. Previously, we had reported that the host epigenetic modulator, histone deacetylase 1 (HDAC1) expression was upregulated on Leishmania donovani infection. This upregulation led to the repression of host defensin genes in response to the infection. In this paper, we have investigated the interplay between the host DOT1L, a histone methyltransferase, and HDAC1 in response to Leishmania donovani infection. We show that the expression of DOT1L is upregulated both at transcript and protein level following infection leading to increase in H3K79me, H3K79me2, and H3K79me3 levels. ChIP experiments showed that DOT1L regulated the expression of HDAC1. Downregulation of DOT1L using siRNA resulted in decreased expression of HDAC1 and increased transcription of defensin genes and thereby, lower parasite load. In turn, HDAC1 regulates the expression of DOT1L on Leishmania donovani infection as downregulation of HDAC1 using siRNA led to reduced expression of DOT1L. Thus, during Leishmania donovani infection, an interplay between DOT1L and HDAC1 regulates the expression of these two histone modifiers leading to downregulation of defensin gene expression.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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