Histone H1 regulates chromatin condensation in Leishmania parasites

Masina, Slavica; Zangger, Haroun; Rivier, D.

doi:10.1016/j.exppara.2006.11.002

Cited by 14 publications

(18 citation statements)

References 16 publications

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“…Toxic properties of histones to microorganisms have been recognized for decades, and histones and histone fragments have been suggested to function as part of an ancient innate immune system present in fish, birds, and mammals (22). It has been shown that histones can kill bacteria (2), and toxicity of histone H1 to L. major promastigotes was recently reported (23). Promastigotes treated with H1 histone showed ultrastructural alterations, such as chromatin changes, cytoplasmic vacuolization, and a rounded appearance (23); this last morphology was also frequently observed in our microscopy studies.…”

Section: Discussionsupporting

confidence: 63%

Leishmania amazonensispromastigotes induce and are killed by neutrophil extracellular traps

Guimarães-Costa

Nascimento²,

Froment³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

502

458

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Neutrophils are short-lived leukocytes that die by apoptosis, necrosis, and NETosis. Upon death by NETosis, neutrophils release fibrous traps of DNA, histones, and granule proteins named neutrophil extracellular traps (NETs), which can kill bacteria and fungi. Inoculation of the protozoan Leishmania into the mammalian skin causes local inflammation with neutrophil recruitment. Here, we investigated the release of NETs by human neutrophils upon their interaction with Leishmania parasites and NETs' ability to kill this protozoan. The NET constituents DNA, elastase, and histones were detected in traps associated to promastigotes by immunofluorescence. Electron microscopy revealed that Leishmania was ensnared by NETs released by neutrophils. Moreover, Leishmania and its surface lipophosphoglycan induced NET release by neutrophils in a parasite number-and dose-dependent manner. Disruption of NETs by DNase treatment during Leishmania-neutrophil interaction increased parasite survival, evidencing NETs' leishmanicidal effect. Leishmania killing was also elicited by NET-rich supernatants from phorbol 12-myristate 13-acetate-activated neutrophils. Immunoneutralization of histone during Leishmania-neutrophil interaction partially reverted Leishmania killing, and purified histone killed the parasites. Meshes composed of DNA and elastase were evidenced in biopsies of human cutaneous leishmaniasis. NET is an innate response that might contribute to diminish parasite burden in the Leishmania inoculation site.histone ͉ protozoa ͉ trypanosomatid

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Section: Discussionsupporting

confidence: 63%

Leishmania amazonensispromastigotes induce and are killed by neutrophil extracellular traps

Guimarães-Costa

Nascimento²,

Froment³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

502

458

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“…However, histone H1 does not colocalize with RNA polymerase II in T. cruzi (data not shown), excluding this possibility. Recently, the superexpression of histone H1 in Leishmania major, another trypanosomatid, was shown to affect cell cycle progression and cellular differentiation (42), in agreement with its role in promoting chromatin condensation (35). The results presented herein raise a novel role for histone H1.…”

supporting

confidence: 63%

Histone H1 of Trypanosoma cruzi Is Concentrated in the Nucleolus Region and Disperses upon Phosphorylation during Progression to Mitosis

2008

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Phosphorylation of histone H1 is intimately related to the cell cycle progression in higher eukaryotes, reaching maximum levels during mitosis. We have previously shown that in the flagellated protozoan Trypanosoma cruzi, which does not condense chromatin during mitosis, histone H1 is phosphorylated at a single cyclin-dependent kinase site. By using an antibody that recognizes specifically the phosphorylated T. cruzi histone H1 site, we have now confirmed that T. cruzi histone H1 is also phosphorylated in a cell cycle-dependent manner. Differently from core histones, the bulk of nonphosphorylated histone H1 in G 1 and S phases of the cell cycle is concentrated in the central regions of the nucleus, which contains the nucleolus and less densely packed chromatin. When cells pass G 2 , histone H1 becomes phosphorylated and starts to diffuse. At the onset of mitosis, histone H1 phosphorylation is maximal and found in the entire nuclear space. As permeabilized parasites preferentially lose phosphorylated histone H1, we conclude that this modification promotes its release from less condensed and nucleolar chromatin after G 2 .The nucleosome, the basic chromatin unit, is assembled by wrapping DNA around an octamer formed by two copies of histone H2A, H2B, H3, and H4 proteins. A fifth histone, called histone H1, packs the chromatin by contacting internucleosomal DNA and the nucleosome particle (50). Histone H1 is formed by a globular domain flanked by a long unstructured C-terminal portion, comprising almost half of the protein, and by a short and also nonstructured N-terminal domain. The C-terminal domain is enriched in basic amino acids that interact with the negative phosphodiester charges of DNA through S/TPKK motifs (26). The globular portion contacts the core histones and the nucleosomal DNA (3), favoring chromatin compaction, which prevents the access of chromatin remodeling factors and therefore restricts transcription and replication (10). Fluorescence recovery after photobleaching experiments have shown that the chromatin residence time of histone H1 is much shorter than that of other histones, suggesting that histone H1 dynamically associates with the nucleosome particles, contributing to several nuclear processes involving chromatin condensation and decondensation (10, 31, 36). However, when histone H1 is absent, chromatin decondenses (20, 47).Histone H1 is phosphorylated at the N-and C-terminal domains in a cell cycle-dependent manner (22). The number of phosphorylated residues is small in G 1 phase and starts to increase when the cell progresses through S and G 2 , reaching a maximal level at mitosis (28). Histone H1 phosphorylation is required for DNA replication (24), and protein kinases that activate replication also promote histone H1 phosphorylation (1). Histone H1 phosphorylation affects the heterochromatin structure (23), DNA repair, chromatin remodeling, apoptosis, and cell aging (29,49). Histone H1 phosphorylation is also involved in chromosome condensation during mitosis. In the absence of histon...

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“…During promastigote growth, histone H1 mRNA progressively accumulates from early log phase to stationary phase. Addition of histone H1 affects chromatin condensation of parasite nuclei and its overexpression in Leishmania has resulted in the reduced infectivity of the parasite in vitro as well as in vivo [35,36]. We observed 1.5-fold upregulation of histone H1 at the RNA level in a resistant isolate and more than 6-fold upregulation at the protein level.…”

Section: Discussionmentioning

confidence: 68%

Overexpression of histone H2A modulates drug susceptibility in Leishmania parasites

Singh¹,

Kumar²,

Duncan³

et al. 2010

International Journal of Antimicrobial Agents

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Histone H1 regulates chromatin condensation in Leishmania parasites

Cited by 14 publications

References 16 publications

Leishmania amazonensispromastigotes induce and are killed by neutrophil extracellular traps

Leishmania amazonensispromastigotes induce and are killed by neutrophil extracellular traps

Histone H1 of Trypanosoma cruzi Is Concentrated in the Nucleolus Region and Disperses upon Phosphorylation during Progression to Mitosis

Overexpression of histone H2A modulates drug susceptibility in Leishmania parasites

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