Transcription factor TFII-I fine tunes innate properties of B lymphocytes

The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here...

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Published in:Frontiers in immunology Vol. 14; p. 1067459
Main Authors: Singh, Amit, Kaileh, Mary, De, Supriyo, Mazan-Mamczarz, Krystyna, Bayarsaihan, Dashzeveg, Sen, Ranjan, Roy, Ananda L.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 23.01.2023
Subjects:
Animals
B cell
Chromatin
chromatin accessibility
FO and MZ B cells
Gtf2i
Humans
Immunology
innate and adaptive immunity
Mice
Protein Binding
Sjogren's Syndrome
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors, TFII - genetics
Transcription Factors, TFII - metabolism
Transcription Factors, TFIII - genetics
Transcription Factors, TFIII - metabolism
B cell
FO and MZ B cells
innate and adaptive immunity
Gtf2i
chromatin accessibility
ISSN:1664-3224, 1664-3224
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Abstract The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
AbstractList The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren's syndrome and Lupus in humans and, germline deletion of the gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for polymorphisms associated with B cell dominated autoimmune diseases in humans.
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren's syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren's syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
Author Singh, Amit
Sen, Ranjan
Bayarsaihan, Dashzeveg
Roy, Ananda L.
Mazan-Mamczarz, Krystyna
Kaileh, Mary
De, Supriyo
AuthorAffiliation 3 Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center , Farmington, CT , United States
1 Laboratory of Molecular Biology and Immunology, National Institutes of Health, National Institute on Aging , Baltimore, MD , United States
2 Laboratory of Genetics & Genomics, National Institutes of Health, National Institute on Aging , Baltimore, MD , United States
AuthorAffiliation_xml – name: 3 Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center , Farmington, CT , United States
– name: 1 Laboratory of Molecular Biology and Immunology, National Institutes of Health, National Institute on Aging , Baltimore, MD , United States
– name: 2 Laboratory of Genetics & Genomics, National Institutes of Health, National Institute on Aging , Baltimore, MD , United States
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  givenname: Mary
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  givenname: Supriyo
  surname: De
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Keywords B cell
FO and MZ B cells
innate and adaptive immunity
Gtf2i
chromatin accessibility
Language English
License Copyright © 2023 Singh, Kaileh, De, Mazan-Mamczarz, Bayarsaihan, Sen and Roy.
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Edited by: Hermann Eibel, University of Freiburg Medical Center, Germany
Reviewed by: Reuben Matthew Tooze, University of Leeds, United Kingdom; Stephen Nutt, The University of Melbourne, Australia
These authors share first authorship
This article was submitted to B Cell Biology, a section of the journal Frontiers in Immunology
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Snippet The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms...
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SubjectTerms Animals
B cell
Chromatin
chromatin accessibility
FO and MZ B cells
Gtf2i
Humans
Immunology
innate and adaptive immunity
Mice
Protein Binding
Sjogren's Syndrome
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors, TFII - genetics
Transcription Factors, TFII - metabolism
Transcription Factors, TFIII - genetics
Transcription Factors, TFIII - metabolism
Title Transcription factor TFII-I fine tunes innate properties of B lymphocytes
URI https://www.ncbi.nlm.nih.gov/pubmed/36756127
https://www.proquest.com/docview/2774897273
https://pubmed.ncbi.nlm.nih.gov/PMC9900109
https://doaj.org/article/e12b30c6e59b4bb0a08d25cb577b1e47
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