Abstract

To understand the mechanism regulating the effector function of memory CD8 T cells, we examined expression and chromatin state of a key transcription factor (eomesodermin, EOMES) and two of its targets: perforin (PRF1) and granzyme B (GZMB). Accessible chromatin associated histone 3 lysine 9 acetylation (H3K9Ac) was found significantly higher at the proximal promoter and the first exon region of all three genes in memory CD8 T cells than in naive CD8 T cells. Correspondingly, EOMES and PRF1 were constitutively higher expressed in memory CD8 T cells than in naive CD8 T cells at resting and activated states. In contrast, higher expression of GZMB was induced in memory CD8 T cells than in naive CD8 T cells only after activation. Regardless of their constitutive or inducible expression, decreased H3K9Ac levels after treatment with a histone acetyltransferase inhibitor (Curcumin) led to decreased expression of all three genes in activated memory CD8 T cells. These findings suggest that H3K9Ac associated accessible chromatin state serves as a corner stone for the differentially high expression of these effector genes in memory CD8 T cells. Thus, epigenetic changes mediated via histone acetylation may provide a chromatin "memory" for the rapid and robust transcriptional response of memory CD8 T cells.

Highlights

  • Why The JI? Submit online. Rapid Reviews! 30 days* from submission to initial decision No Triage! Every submission reviewed by practicing scientists Fast Publication! 4 weeks from acceptance to publicatio

  • We showed that the effector function regulator (EOMES) and two of its targets (PRF1 and granzyme B (GZMB)) are expressed at a higher level in memory CD8 T cells than in naive CD8 T cells in the resting stage and/or after activation

  • The significant higher levels of H3K9Ac were observed in the EOMES, PRF1, and GZMB loci in memory CD8 T cells compared with naive CD8 T cells

Read more

Summary

Abbrevations used in this paper

HAT, histone acetyltransferase; PRF1, perforin 1; GZMB, granzyme B; HDAC, histone deacetylase; ChIP, chromatin immunoprecipitation. The levels of H3K9Ac in the EOMES, PRF1, and GZMB loci were higher, at the transcription start site, in memory cells than in naive cells. Induced hypoacetylation in these gene loci by a HAT inhibitor (curcumin) resulted in decreased expressions of EOMES, PRF1, and GZMB in memory cells in response to in vitro stimulation. These findings suggest that histone acetylation is essential in determining the level of EOMES, PRF1, and GZMB expressions in memory CD8 T cells

Materials and Methods
Results
Discussion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.