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PMID: 16183743 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Intramural Research Support, U.S. Gov't, P.H.S.

Partner-regulated interaction of IFN regulatory factor 8 with chromatin visualized in live macrophages.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 40 ·2005-10-04 ·Pages 14368-73

Laricchia-Robbio L, Tamura T, Karpova T, Sprague BL, McNally JG, Ozato K

Abstract

IFN regulatory factor (IRF) 8 is a transcription factor that directs macrophage differentiation. By fluorescence recovery after photobleaching, we visualized the movement of IRF8-GFP in differentiating macrophages. Recovery data fitted to mathematical models revealed two binding states for IRF8. The majority of IRF8 was highly mobile and transiently interacted with chromatin, whereas a small fraction of IRF8 bound to chromatin more stably. IRF8 mutants that did not stimulate macrophage differentiation showed a faster recovery, revealing little interaction with chromatin. A macrophage activation signal by IFN-gamma/LPS led to a global slowdown of IRF8 movement, leading to increased chromatin binding. In fibroblasts where IRF8 has no known function, WT IRF8 moved as fast as the mutants, indicating that IRF8 does not interact with chromatin in these cells. However, upon introduction of IRF8 binding partners, PU.1 and/or IRF1, the mobility of IRF8 was markedly reduced, producing a more stably bound component. Together, IRF8-chromatin interaction is dynamic in live macrophages and influenced by partner proteins and immunological stimuli.

MeSH Terms
Animals Cell Line Chromatin/metabolism Fluorescence Recovery After Photobleaching Green Fluorescent Proteins Interferon Regulatory Factors/immunology,metabolism Interferon-gamma/metabolism Macrophages/immunology Mice Models, Biological Protein Binding Transcription Factors/immunology,metabolism
Chemicals
Chromatin Interferon Regulatory Factors Transcription Factors interferon regulatory factor-8 Green Fluorescent Proteins Interferon-gamma
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Laricchia-Robbio Leopoldo
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2753, USA.
Tamura Tomohiko
Karpova Tatiana
Sprague Brian L
McNally James G
Ozato Keiko
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0504014102
Published
2005-10-04
Epub
2005-00-23
Pages
14368-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1242294
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1073/pnas.0504014102 PMC Full Text View journal details
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