Jason Lieb

The DNA sequence information in the human genome is read and interpreted by proteins. Without interactions between proteins and DNA, life would not exist. The Lieb lab studies how and where proteins interact with the genome on a global scale, and how these interactions affect the biology of living cells. One of the most important tools used in the laboratory is the DNA microarray, a simple but powerful research tool that can be used to track the level of every RNA message in a cell, and at the same time create high-resolution, genome-wide maps of protein-DNA interactions. In particular, the lab concentrates on four areas:

1. What rules do DNA-associated proteins use to bind their genomic targets in vivo?

2. How is genomic DNA sequence information organized in a cell’s nucleus? How is accessibility to that information regulated for sequences with different biological functions, for example regulatory versus coding sequence?

3. Does the organization of the genome, particularly differences in chromatin, affect these rules and allow protein-genome interactions regulated so they occur at the proper time, and in the proper tissues?

4. What are the functional consequences of protein-genome interactions, especially with regard to specifying transcriptional programs?
The Lieb lab aims to answer these questions using the yeast S. cerevisiae, the most experimentally tractable eukaryote, and the nematode C. elegans, one of the simplest metazoans.

Selected Publications:
Ercan S, Giresi PG, Whittle CM, Zhang X, Green RD, Lieb JD. (2007) X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation. Nat Genet. 39:403-8.

Giresi PG, Kim J, McDaniell RM, Iyer VR, Lieb JD. (2006) FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. Dec 19; [Epub ahead of print]

Buck MJ, Lieb JD. (2006) A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat Genet. 38:1446-51.

Hogan GJ, Lee CK, Lieb JD. (2006) Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters. PLoS Genet. 2(9):e158.

Rao B, Shibata Y, Strahl BD, Lieb JD. (2005) Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide. Mol Cell Biol 25:9447-59.

Liu X, Noll DM, Lieb JD, Clarke ND. (2005) DIP-chip: Rapid and accurate determination of DNA-binding specificity. Genome Res 15:421-427.

Lee CK, Shibata Y, Rao B, Strahl BD and Lieb JD (2004) Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36:900-905.

Nagy PL, Cleary M, Brown PO and Lieb JD. (2003) Genomewide demarcation of RNA polymerase II transcription units revealed by physical fractionation of chromatin. Proc Natl Acad Sci USA 100:6364-6369.








				The DNA sequence information in the human genome is read and interpreted by proteins. Without interactions between proteins and DNA, life would not exist. The Lieb lab studies how and where proteins interact with the genome on a global scale, and how these interactions affect the biology of living cells. One of the most important tools used in the laboratory is the DNA microarray, a simple but powerful research tool that can be used to track the level of every RNA message in a cell, and at the same time create high-resolution, genome-wide maps of protein-DNA interactions. In particular, the lab concentrates on four areas: 1. What rules do DNA-associated proteins use to bind their genomic targets in vivo? 2. How is genomic DNA sequence information organized in a cell’s nucleus? How is accessibility to that information regulated for sequences with different biological functions, for example regulatory versus coding sequence? 3. Does the organization of the genome, particularly differences in chromatin, affect these rules and allow protein-genome interactions regulated so they occur at the proper time, and in the proper tissues? 4. What are the functional consequences of protein-genome interactions, especially with regard to specifying transcriptional programs? The Lieb lab aims to answer these questions using the yeast S. cerevisiae, the most experimentally tractable eukaryote, and the nematode C. elegans, one of the simplest metazoans. Selected Publications: Ercan S, Giresi PG, Whittle CM, Zhang X, Green RD, Lieb JD. (2007) X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation. Nat Genet. 39:403-8. Giresi PG, Kim J, McDaniell RM, Iyer VR, Lieb JD. (2006) FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. Dec 19; [Epub ahead of print] Buck MJ, Lieb JD. (2006) A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat Genet. 38:1446-51. Hogan GJ, Lee CK, Lieb JD. (2006) Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters. PLoS Genet. 2(9):e158. Rao B, Shibata Y, Strahl BD, Lieb JD. (2005) Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide. Mol Cell Biol 25:9447-59. Liu X, Noll DM, Lieb JD, Clarke ND. (2005) DIP-chip: Rapid and accurate determination of DNA-binding specificity. Genome Res 15:421-427. Lee CK, Shibata Y, Rao B, Strahl BD and Lieb JD (2004) Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36:900-905. Nagy PL, Cleary M, Brown PO and Lieb JD. (2003) Genomewide demarcation of RNA polymerase II transcription units revealed by physical fractionation of chromatin. Proc Natl Acad Sci USA 100:6364-6369.


	contact information: [phone] (919) 843-3228 [email] [website]