Epigenetic programming of monocytetomacrophage differentiation and trained innate

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity Dan Pensinger 2/17/15

Outline • Background – Eukaryotic DNA Structure and Regulation – Epigenetics – Macrophage differentiation and signaling – Techniques used in the paper • Results • Summary

Eukaryotic DNA Structure and Regulation Genome, Smithsonian National Musuem of Natural History

Eukaryotic DNA Structure and Regulation Lawerence Berkeley National Laboratory

Epigenetic Histone Modifications The Alberta Epigenetics Network

Epigenetic Histone Modifications The Alberta Epigenetics Network

Epigenetic Histone Modifications The Alberta Epigenetics Network

Epigenetic Histone Modifications Acetyl K 27 H 3 K 27 Ac promoters and enhancers

Macrophage Differentiation and Signaling Siamon Gordon Nature Reviews Immunology 2003

Macrophage Differentiation and Signaling LPS Medvedev et al. J Endotoxin Res. 2006

Macrophage Differentiation and Signaling Invivogen

Cyclic AMP Signaling

Outline • Background – Eukaryotic DNA Structure and Regulation – Epigenetics – Macrophage differentiation and signaling – Techniques used in the paper • Results • Summary

Paper Overview

Monocyte Isolation Miltenyi

Chromatin Immuno Precipitation (Ch. IP) Seq wikipedia

RNA-Seq Brian Haas and Micheal Zody, Nature Biotechnology 2010

DNase Seq Wang et al. PLo. SOne 2012

Paper Overview

Figure 1

Figure 1 Acetyl K 27 H 3 K 27 Ac promoters and enhancers

Figure 1 P and E Enhancers Promoters

Figure 1

Figure 1

Figure 1

Figure 1

Figure 2

Figure 2 All MF MF MO LPS-MF BG-MF

Figure 2

Figure 2 All MF MO/LPS-MF BG-MF

Figure 2

Figure 2 BGMF LPSMF MO MF

Figure 2

Figure 3

Figure 3

BGMF LPS-MF MF All MF MO BG-MF All MF MO/LPS-MF BG-MF Figure 3

Figure 4

Figure 4 ACe 1 = BG-MF ACe 2 = MO ACe 3 = All MF ACe 4 = MF ACe 5 = LPS-MF

Figure 5

Figure 5 β-Glucan

Figure 5

Paper Overview