Jmjd3 contributes to the control of gene expression in LPS-activated macrophages.
Jmjd3, a JmjC family histone demethylase, is induced by the transcription factor NF-kB in response to microbial stimuli. Jmjd3 erases H3K27me3, a histone mark associated with transcriptional repression and involved in lineage determination. However, the specific contribution of Jmjd3 induction and H3K27me3 demethylation to inflammatory gene expression remains unknown. Using chromatin immunoprecipitation-sequencing we found that Jmjd3 is preferentially recruited to transcription start sites characterized by high levels of H3K4me3, a marker of gene activity, and RNA polymerase II (Pol_II). Moreover, 70% of lipopolysaccharide (LPS)-inducible genes were found to be Jmjd3 targets. Although most Jmjd3 target genes were unaffected by its deletion, a few hundred genes, including inducible inflammatory genes, showed moderately impaired Pol_II recruitment and transcription. Importantly, most Jmjd3 target genes were not associated with detectable levels of H3K27me3, and transcriptional effects of Jmjd3 absence in the window of time analysed were uncoupled from measurable effects on this histone mark. These data show that Jmjd3 fine-tunes the transcriptional output of LPS-activated macrophages in an H3K27 demethylation-independent manner.
De Santa
Francesca
F
Department of Experimental Oncology, European Institute of Oncology (IEO), IFOM-IEO Campus, Milan, Italy.
Narang
Vipin
V
Yap
Zhei Hwee
ZH
Tusi
Betsabeh Khoramian
BK
Burgold
Thomas
T
Austenaa
Liv
L
Bucci
Gabriele
G
Caganova
Marieta
M
Notarbartolo
Samuele
S
Casola
Stefano
S
Testa
Giuseppe
G
Sung
Wing-Kin
WK
Wei
Chia-Lin
CL
Natoli
Gioacchino
G
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D056484:Jumonji Domain-Containing Histone Demethylases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice
D008070:Lipopolysaccharides; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse