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Identification of Histone H3 and H4 Amino Acid Residues Important for the Regulation of Arsenite Stress Signaling in Saccharomyces cerevisiae
journal contribution
posted on 2020-02-07, 21:43 authored by Pilendra
Kumar Thakre, Upendarrao Golla, Ashis Biswas, Raghuvir Singh TomarArsenic
is an environmental carcinogen that causes many diseases
in humans, including cancers and organ failures, affecting millions
of people in the world. Arsenic trioxide is a drug used for the treatment
of acute promyelocytic leukemia (APL). In the present study, we screened
the synthetic histone H3 and H4 library in the presence of arsenite
to understand the role of histone residues in arsenic toxicity. We
identified residues of histone H3 and H4 crucial for arsenite stress
response. The residues H3T3, H3G90, H4K5, H4G13, and H4R95 are required
for the activation of Hog1 kinase in response to arsenite exposure.
We showed that a reduced level of Hog1 activation increases the intracellular
arsenic content in these histone mutants through the Fps1 channel.
We have also noticed the reduced expression of ACR3 exporter in the mutants. The growth defect of mutants caused by
arsenite exposure was suppressed in hyperosmotic conditions, in a
higher concentration of glucose, and upon deletion of the FPS1 gene. The arsenite sensitive histone mutants also showed
a lack of H3K4 methylation and reduced H4K16 acetylation. Altogether,
we have identified the key residues in histone H3 and H4 proteins
important for the regulation of Hog1 signaling, Fps1 activity, and ACR3 expression during arsenite stress.
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Keywords
Fps 1 channelHog 1 kinasearsenite stress responseresidues H 3T H 3G H 4K H 4GAPLH 4K acetylationH 4 libraryH 3K methylationFps 1 activityHog 1 activation increasesH 4 AminoHistone H 3H 4 proteinsSaccharomyces cerevisiae Arsenicarsenite exposureACR 3 exporterhistone mutantsArsenite Stress Signalingintracellular arsenic contentFPS 1 gene4Rhistone H 3ACR 3 expression
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