Gang Wei^1,7, Lai Wei^2,7, Jinfang Zhu⁴, Chongzhi Zang⁵, Jane Hu-Li⁴, Zhengju Yao², Kairong Cui¹, Yuka Kanno², Tae-Young Roh^1,6, Wendy T. Watford², Dustin E. Schones¹, Weiqun Peng⁵, Hong-wei Sun³, William E. Paul⁴, John J. O'Shea^2*, and Keji Zhao^1*

¹ Laboratory of Molecular Immunology, NHLBI, NIH, Bethesda, MD 20892, USA
² Molecular Immunology and Inflammation Branch, NIH, Bethesda, MD 20892, USA

³ Biodata Mining and Discovery Section, NIAMS, NIH, Bethesda, MD 20892, USA

⁴ Laboratory of Immunology, NIAID, NIH, Bethesda, MD 20892, USA

⁵ Department of Physics, George Washington University, Washington, DC, 20052, USA

⁶ Current address: Division of Molecular and Life Science, POSTECH, Pohang, 790-784, Republic of Korea

⁷ These authors contribute equally to this work

^* Corresponding authors.

Summary

Multipotential naïve CD4⁺ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4⁺ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naïve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFNγ induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4⁺ T helper cell differentiation.

Data

Information on file formats

Tag coordinate bed files -- contain coordinates for all uniquely mapped reads for each experiment. Each line is in the format:

Summary bed files -- Bed files displaying the number of uniquely mapped reads in 200 bp windows. All read start coordinates are adjusted by 75 bp in the direction of the strand they map to before summing is done. The file is actually in bedGraph format that is acceptable by UCSC genome browser. User could upload the gz files to the "Manage Custom tracks" and visualize the tag numbers in UCSC genome browser. After downloading the summary bed files and saving on your PC, the steps to visualize the files are 1) go to UCSC Genome Browser Homepage and click the "Genome Browser" shown on the top left page; 2) chose genome "Mouse", assembly (mm8) and submit; 3) find the "manage Custom tracks" button (right below the shown tracks) and click to get into the "manage customer tracks" web page; 4) find the "add customer tracks" and click to get into a page where you can upload the files; 5) use the "Browse..." button to locate your interested summary file (gz format is acceptable) and click "Submit"; 6) after uploading, the page will be directed back to the "manage customer tracks" web page, find the "go to genome browser" button and click and then you will get the tracks, or repeat step 4)-6) to upload more tracks.

(Note: all coordinates are from the Mouse Feb. 2006 (mm8) assembly)