The focus of our research is on how the epigenome controls cell fates. One genome encodes the cellular functions for over 200 human cell types. We think the remarkable cellular specificities of different tissue/cell types within an individual are largely controlled by the epigenome. Epigenetic marks, including histone tail modifications and DNA methylation, are key identifiers of transcriptional output, and provide unique signatures of cellular identity. Using high-throughput experimental and computational technologies, we are trying to determine how the epigenome 1) confers pluripotency in hESCs and iPSCs; 2) controls transcription and cellular differentiation; and 3) provides a basis for many disease states. Similarly, we are trying to understand the consequences of epigenetic abnormalities in iPSCs.
In addition, histone modifications provide a remarkable means for annotating the genome. We and others have shown that histone modifications can identify cell-specific enhancer elements, promoter elements and regions of transcribed RNAs. We are continuing to develop unique epigenetic signatures throughout the human genome to better understand the aforementioned elements, and remaining “junk” DNA.
Egelhofer TA†, Minoda A†, Klugman S†, Kolasinska-Zwierz P, Alekseyenko AA, Cheung MS, Day DS, Gadel, S, Gorchakov, AA, Gu T, Kharchenko PV, Kuan, S, Latorre I, Linder-Basso D, Luu Y, Ngo Q, Perry M, Rechtsteiner A, Riddle NC, Schwartz YB, Shanower GA, Vielle A, Ahringer J, Elgin SCR, Kuroda MI, Pirrotta V, Ren B, Strome S, Park PJ^, Karpen G^, Hawkins RD^, and Lieb JD^ (2010) Assessment of histone-modification antibody quality. Nature Structural & Molecular Biology. Accepted. ^Co-corresponding Authors.
Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, Johnson BE, Fouse SD, Delaney A, Zhao Y, Olshen A, Ballinger T, Zhou X, Forsberg KJ, Gu J, Echipare L, O'Geen H, Lister R, Pelizzola M, Xi Y, Epstein CB, Bernstein BE, Hawkins RD, Ren B, Chung WY, Gu H, Bock C, Gnirke A, Zhang MQ, Haussler D, Ecker JR, Li W, Farnham PJ, Waterland RA, Meissner A, Marra MA, Hirst M, Milosavljevic A, Costello JF. (2010) Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nature Biotechnology. 28(10), 852-862
Elo LL†, Järvenpää H†, Tuomela S†, Raghav S†, Ahlfors H, Laurila K, Gupta B, Lund RJ, Tahvanainen J, Hawkins RD, Oresic M, Lähdesmäki H, Rasool O, Rao KV, Aittokallio T, Lahesmaa R. (2010) Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity 32: 852-862.
Hawkins RD†, Hon GC†, Ren B. (2010) Next-Generation Genomics: An Integrative Approach. Nature Reviews Genetics 11(7); 476-486.
Hawkins RD†, Hon GC †, Lee LK, Ngo Q, Lister R, Pelizzola M, Kuan S, Edsall LE, Ye Z, Espinoza C, Antosiewicz-Bourget J, Agarwahl S, Shen L, Ruotti V, Wang W, Stewart R, Thomson JA, Ecker JR, Ren B. (2010) Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6: 279-491.
Lister R†, Pelizzola M†, Dowen RH, Hawkins RD, Hon GC, Tonti-Filippini J, Nery JR, Lee LK, Edsall LE, Antosiewicz-Bourget J, Ruotti V, Elwell A, Hernandez A, Stewart R, Millar AH, Thomson JA, Ren B, Ecker JR. (2009) Human DNA methylomes at single-base resolution reveal widespread cell-specific epigenetic signatures. Nature 462: 315-322.
Hon GC, Hawkins RD, Ren B. (2009) Predictive chromatin signatures in the mammalian genome. Hum Mol Genet.18(R2): R195-201.(Review)
Heintzman ND†, Hon G†, Hawkins RD†, Kheradpour P, Ching KA, Stuart RK, Harp LF, Ching CW, Liu H, Zhang X, Green RD, Crawford GE, Kellis M, and Ren B. (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459: 108-112.
†Equal contribution of work