Download ID2 is required for binding of BATF/AP-1

ID2 is required for binding of BATF/AP-1-related family transcription factors to
genes associated with NK cell effector maturation
Barbara L. Kee, Yiying Xu, Erin C. Zook, Renee dePooter, and Zhong-Yin Li.
Dept. of Pathology and Committee on Immunology, University of Chicago, Chicago IL
USA, 60615.
Id2 is an inhibitor of the E protein transcription factors that is required for the
development of mature NK cells. Here we show that mature NK cells develop in the
absence of Id2 but fail to progress from the naïve KLRG1-CD27+CD11b- stage to the
effector KLRG1+CD27-CD11b+ stage. The cytotoxic effector program that characterizes
this transition, including transcription of Gzmb Il18r1, Il1rl1, Ifng and Prf1, is not initiated
in the absence of Id2. Instead, Id2-deficient naïve NK cells up-regulate expression of
multiple T lymphocyte associated transcripts encoding cytokine and chemokine
receptors as well as intracellular signaling proteins. A transposase accessible chromatin
(ATAC)-seq analysis revealed an increase in open chromatin at E protein binding sites in
upregulated genes confirming heightened E protein activity. In contrast, in the absence
of Id2 there was a loss of open chromatin at NK cell effector genes that was associated
with sequences bound by signal regulated transcription factors of the BATF/AP-1 family.
Our data reveal a possible role for BATF/AP-1 transcription factors in naïve NK cells to
promote the expression of the cytotoxic effector program of mature NK cells.
Sessions: NK cell development and differentiation, Innate lymphoid cells.