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Cited by 25Genomics and Chromatin DynamicsT-cell and B-cell ImmunologyEpigenetics and DNA Methylation

PU.1 as a chromatin accessibility factor for immunoglobulin genes

Marecki, Sylvia, McCarthy, Kevin M, Nikolajczyk, Barbara S·2004·Molecular Immunology
DOI 10.1016/j.molimm.2003.08.007
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Abstract

The hematopoietic-specific transcription factor PU.1 is a chromatin accessibility factor, based on analysis of the immunoglobulin heavy chain intronic (mu) enhancer. Whether PU.1 functions as an accessibility factor for additional PU.1-regulated genes is unknown. Outside the constraints of chromatin, PU.1 binds and activates transcription through both mu and kappa3' immunoglobulin enhancers, among others. The DNA-binding ETS domain of PU.1 is sufficient for activating both enhancers in an extrachromosomal context. New data show that the ETS domain of PU.1 is sufficient for increasing accessibility of a closed mu enhancer chromatin structure proximal to the PU.1-binding site. In contrast, PU.1 does not alter widespread chromatin accessibility. Furthermore, PU.1 does not induce accessibility proximal or distal to its binding site on the kappa3' enhancer. Taken together the data demonstrate that PU.1 induces chromatin accessibility proximal to its binding site at a locus activated early in development, the mu locus. PU.1 does not function as an accessibility factor for the kappa3' enhancer, which regulates a locus important for later stages of B cell development. We conclude that PU.1 is a context-dependent chromatin accessibility factor that, alone, cannot establish widespread accessibility required for critical developmental processes such as antigen receptor recombination.

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  • PU.1 has chromatin opening activity in B cells, can eject nucleosomes in macrophage lines, and causes rapid increases in ATAC accessibility at sites it occupies when introduced into Scid.adh.2C2 cells.

    “This is consistent with PU.1's activity as a site-specific chromatin opening factor in B cells (96, 97), with the ability of PU.1 to eject nucleosomes from sites where it binds in macrophage lines (12), and with its ability to cause rapid increases in ATAC accessibility at the sites it occupies when introduced into Scid.adh.2C2 cells (85).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [97]

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Authors
Marecki, S., McCarthy, K. M., & Nikolajczyk, B. S.
Affiliations
Boston University (US)
Corresponding author
Nikolajczyk, Barbara S
ORCID
Nikolajczyk, Barbara S
Venue
Molecular Immunology
Publisher
Elsevier BV
Published
2004-01
Volume
40
Issue
10
Pages
723-731
ISSN
0161-5890 (ISSN-L)
DOI
10.1016/j.molimm.2003.08.007
OpenAlex
W2048265614
Cited by
25
References
5
Citations by year
2019: 2 · 2018: 3 · 2013: 2
FWCI
1.50
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Arthritis Foundation
  • National Institutes of Health
  • National Cancer Institute (T32 CA-64070, T32CA064070)
  • National Institute of Allergy and Infectious Diseases (R01AI054611, R01AI54611)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
PU.1, chromatin accessibility, ETS domain, transcriptional activation, B cell development, hematopoietic transcription factors
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Binding Sites, Cell Line, Chromatin, Enhancer Elements, Genetic, Genes, Immunoglobulin, Immunoglobulin mu-Chains, Proto-Oncogene Proteins, T-Lymphocytes, Trans-Activators, Protein Structure, Tertiary, DNA, Complementary, NIH 3T3 Cells, Mice

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