Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits

ABSTRACT Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor composed of three subunits, namely, NF-YA, NF-YB, and NF-YC, which are conserved throughout evolution. In higher eukaryotes, NF-Y plays important roles in several cellular processes (development, cell cycle regulation, apoptos...

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Autores principales:	Dipak Manna, Upinder Singh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Entamoeba developmental biology encystation transcription factor transcriptional regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c91de908edd34e1fb677d549ccaabd6d
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spelling	oai:doaj.org-article:c91de908edd34e1fb677d549ccaabd6d2021-11-15T15:55:25ZNuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits10.1128/mBio.00737-192150-7511https://doaj.org/article/c91de908edd34e1fb677d549ccaabd6d2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00737-19https://doaj.org/toc/2150-7511ABSTRACT Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor composed of three subunits, namely, NF-YA, NF-YB, and NF-YC, which are conserved throughout evolution. In higher eukaryotes, NF-Y plays important roles in several cellular processes (development, cell cycle regulation, apoptosis, and response to growth, stress, and DNA damage) by controlling gene expression through binding to a CCAAT promoter motif. We demonstrated that NF-Y subunits in the protist Entamoeba, while significantly divergent from those of higher eukaryotes, have well-conserved domains important for subunit interactions and DNA binding and that NF-YB and NF-YC are developmentally expressed during encystation. Electrophoretic mobility shift assays confirmed that the NF-Y protein(s) from Entamoeba cysts binds to a CCAAT motif. Consistent with a role as a transcription factor, the NF-Y proteins show nuclear localization during development. Additionally, we demonstrated that NF-YC localizes to the chromatoid body (an RNA processing center) during development, indicating that it may have a role in RNA processing. Finally, silencing of the NF-YC subunit resulted in reduced stability of the NF-Y complex and decreased encystation efficiency. We demonstrated that the NF-Y complex functions at a time point subsequent to the NAD+ flux and expression of the transcription factor encystation regulatory motif-binding protein, both of which are early regulators of Entamoeba development. Taken together, our results demonstrate that the NF-Y complex plays an important role in regulating encystation in Entamoeba and add to our understanding of the transcriptional networks and signals that control this essential developmental pathway in an important human pathogen. IMPORTANCE The human parasite Entamoeba histolytica is an important pathogen with significant global impact and is a leading cause of parasitic death in humans. Since only the cyst form can be transmitted, blocking encystation would prevent new infections, making the encystation pathway an attractive target for the development of new drugs. Identification of the genetic signals and transcriptional regulatory networks that control encystation would be an important advance in understanding the developmental cascade. We show that the Entamoeba NF-Y complex plays a crucial role in regulating the encystation process in Entamoeba.Dipak MannaUpinder SinghAmerican Society for MicrobiologyarticleEntamoebadevelopmental biologyencystationtranscription factortranscriptional regulationMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Entamoeba developmental biology encystation transcription factor transcriptional regulation Microbiology QR1-502
spellingShingle	Entamoeba developmental biology encystation transcription factor transcriptional regulation Microbiology QR1-502 Dipak Manna Upinder Singh Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
description	ABSTRACT Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor composed of three subunits, namely, NF-YA, NF-YB, and NF-YC, which are conserved throughout evolution. In higher eukaryotes, NF-Y plays important roles in several cellular processes (development, cell cycle regulation, apoptosis, and response to growth, stress, and DNA damage) by controlling gene expression through binding to a CCAAT promoter motif. We demonstrated that NF-Y subunits in the protist Entamoeba, while significantly divergent from those of higher eukaryotes, have well-conserved domains important for subunit interactions and DNA binding and that NF-YB and NF-YC are developmentally expressed during encystation. Electrophoretic mobility shift assays confirmed that the NF-Y protein(s) from Entamoeba cysts binds to a CCAAT motif. Consistent with a role as a transcription factor, the NF-Y proteins show nuclear localization during development. Additionally, we demonstrated that NF-YC localizes to the chromatoid body (an RNA processing center) during development, indicating that it may have a role in RNA processing. Finally, silencing of the NF-YC subunit resulted in reduced stability of the NF-Y complex and decreased encystation efficiency. We demonstrated that the NF-Y complex functions at a time point subsequent to the NAD+ flux and expression of the transcription factor encystation regulatory motif-binding protein, both of which are early regulators of Entamoeba development. Taken together, our results demonstrate that the NF-Y complex plays an important role in regulating encystation in Entamoeba and add to our understanding of the transcriptional networks and signals that control this essential developmental pathway in an important human pathogen. IMPORTANCE The human parasite Entamoeba histolytica is an important pathogen with significant global impact and is a leading cause of parasitic death in humans. Since only the cyst form can be transmitted, blocking encystation would prevent new infections, making the encystation pathway an attractive target for the development of new drugs. Identification of the genetic signals and transcriptional regulatory networks that control encystation would be an important advance in understanding the developmental cascade. We show that the Entamoeba NF-Y complex plays a crucial role in regulating the encystation process in Entamoeba.
format	article
author	Dipak Manna Upinder Singh
author_facet	Dipak Manna Upinder Singh
author_sort	Dipak Manna
title	Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
title_short	Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
title_full	Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
title_fullStr	Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
title_full_unstemmed	Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits
title_sort	nuclear factor y (nf-y) modulates encystation in <italic toggle="yes">entamoeba</italic> via stage-specific expression of the nf-yb and nf-yc subunits
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/c91de908edd34e1fb677d549ccaabd6d
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Nuclear Factor Y (NF-Y) Modulates Encystation in <italic toggle="yes">Entamoeba</italic> via Stage-Specific Expression of the NF-YB and NF-YC Subunits

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