Nucleosomes are stably evicted from enhancers but not promoters upon induction of certain pro-inflammatory genes in mouse macrophages.
Chromatin is thought to act as a barrier for binding of cis-regulatory transcription factors (TFs) to their sites on DNA and recruitment of the transcriptional machinery. Here we have analyzed changes in nucleosome occupancy at the enhancers as well as at the promoters of three pro-inflammatory genes when they are induced by bacterial lipopolysaccharides (LPS) in primary mouse macrophages. We find that nucleosomes are removed from the distal enhancers of IL12B and IL1A, as well as from the distal and proximal enhancers of IFNB1, and that clearance of enhancers correlates with binding of various cis-regulatory TFs. We further show that for IFNB1 the degree of nucleosome removal correlates well with the level of induction of the gene under different conditions. Surprisingly, we find that nucleosome occupancy at the promoters of IL12B and IL1A does not change significantly when the genes are induced, and that a considerably fraction of the cells is occupied by nucleosomes at any given time. We hypothesize that competing nucleosomes at the promoters of IL12B and IL1A may play a role in limiting the size of transcriptional bursts in individual cells, which may be important for controlling cytokine production in a population of immune cells.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
Alison
A
Gjidoda
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
Mohita
M
Tagore
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
Michael J
MJ
McAndrew
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
Alexander
A
Woods
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.
Monique
M
Floer
D000818:Animals; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism
D006657:Histones; D053762:Interleukin-12 Subunit p40; D053582:Interleukin-1alpha; D008070:Lipopolysaccharides; D009707:Nucleosomes; D014157:Transcription Factors; D016899:Interferon-beta