HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells.
The activation of naïve B lymphocyte involves rapid and major changes in chromatin organization and gene expression; however, the complete repertoire of nuclear factors affecting these genomic changes is not known. We report that HMGN proteins, which bind to nucleosomes and affect chromatin structure and function, co-localize with, and maintain the intensity of DNase I hypersensitive sites genome wide, in resting but not in activated B cells. Transcription analyses of resting and activated B cells from wild-type and Hmgn(-/-) mice, show that loss of HMGNs dampens the magnitude of the transcriptional response and alters the pattern of gene expression during the course of B-cell activation; defense response genes are most affected at the onset of activation. Our study provides insights into the biological function of the ubiquitous HMGN chromatin binding proteins and into epigenetic processes that affect the fidelity of the transcriptional response during the activation of B cell lymphocytes.
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shaofei
S
Zhang
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20892, USA.
Iris
I
Zhu
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tao
T
Deng
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Takashi
T
Furusawa
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mark
M
Rochman
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Melanie S
MS
Vacchio
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Remy
R
Bosselut
Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
Arito
A
Yamane
Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
Rafael
R
Casellas
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20892, USA landsman@ncbi.nlm.nih.gov.
David
D
Landsman
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA bustin@helix.nih.gov.
Michael
M
Bustin
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D024001:HMGN Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024241:HMGN1 Protein / Q000378:metabolism; D024242:HMGN2 Protein / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D002843:Chromatin; D024001:HMGN Proteins; D024241:HMGN1 Protein; D024242:HMGN2 Protein; D009707:Nucleosomes; D003850:Deoxyribonuclease I