Chromatin Regulation in Development
Our histone modification ChIP-seq and gene expression (RNA-seq) data (UCSC Genome Browser screenshot)
Welcome to the Saltzman lab webpage!
Our lab is interested in the role of chromatin regulation in establishing and maintaining the gene expression differences that underlie cellular identity. We focus on a versatile family of chromatin ‘readers’ that recognize methylated lysine residues on the N-terminal ‘tail’ of histone H3 and function as components of multi-protein chromatin-modification complexes. Chromatin readers can mediate the silencing of genes encoding key regulators of development and proliferation and therefore play roles in the self-renewal and differentiation of embryonic and somatic stem cells. We will investigate:
- What determines the genomic binding sites of chromatin readers?
- What roles do chromatin readers play in the inheritance of gene expression states?
- How are related chromatin readers specialized for cell type- and context-specific functions?
These fundamental questions will help us to understand the roles of chromatin regulation in the development of a single cell into a mature organism and how improper control of this process can lead to disease.
We employ a combination of genomics, cell biology and genetics approaches to address these questions using the tiny roundworm, Caenorhabditis elegans, as a model organism.
The worm is transparent, grows quickly, has hundreds of progeny, and the lineages and fates of all its 959 somatic cells have been mapped (see the collection of references at WormAtlas). In addition, many genetic pathways are conserved with humans, making it a simplified yet advantageous system to understand chromatin regulation in the context of a whole organism.
Model organism, C. elegans
Nuclei of isolated C. elegans germline (DAPI staining)
Additional area of interest include:
- Chromatin and non-coding RNA regulation in development
- Unconventional RNA-binding proteins
- Cell type-specific phenotypes of mutations in core gene expression machinery
Aram, R., MacGillivray, K., Li, C., Saltzman, A.L. (2019). Tools for Mos1-mediated single copy insertion (mosSCI) with excisable unc-119(+) or NeoR (G418) selection cassettes. microPublication Biology. 10.17912/micropub.biology.000146.
Perales R., Pagano D., Wan G., Fields B.D., Saltzman A.L., Kennedy S.G. (2018). Transgenerational Epigenetic Inheritance Is Negatively Regulated by the HERI-1 Chromodomain Protein. Genetics. doi:10.1534/genetics.118.301456. PMID: 30389807. PMCID: PMC6283161.
Saltzman A.L., Soo M.A. Aram, R. and Lee J.T. (2018). Multiple Histone Methyl-Lysine Readers Ensure Robust Development and Germline Immortality in Caenorhabditis elegans. Genetics 210(3): 907-923. doi.org/10.1534/genetics.118.301518. PMID: 30185429. PMCID: PMC6218232.
Previous Work (pre- C. elegans)
Saltzman, A.L., Pan, Q., and Blencowe, B.J. (2011). Regulation of alternative splicing by the core spliceosomal machinery. Genes Dev 25: 373-384. PMID: 21325135. PMCID: PMC3042160.
Saltzman, A.L., Kim, Y.K., Pan, Q., Fagnani, M.M., Maquat, L.E., and Blencowe, B.J. (2008). Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay. Mol Cell Biol 28: 4320-4330. PMID: 18443041. PMCID: PMC2447145.
Fagnani, M., Barash, Y., Ip, J.Y., Misquitta, C., Pan, Q., Saltzman, A.L., Shai, O., Lee, L., Rozenhek, A., Mohammad, N., Willaime-Morawek, S., Babak, T., Zhang, W., Hughes, T. R., van der Kooy, D., Frey, B. J., and Blencowe, B. J. (2007). Functional coordination of alternative splicing in the mammalian central nervous system. Genome Biol 8: R108. PMID: 17565696. PMCID: PMC2394768.
Pan, Q.*, Saltzman, A.L.*, Kim, Y.K., Misquitta, C., Shai, O., Maquat, L.E., Frey, B.J., and Blencowe, B.J. (2006). Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression. Genes Dev 20: 153-158. PMID: 16418482. PMCID: PMC1356107.
Pan, Q., Shai, O., Misquitta, C., Zhang, W., Saltzman, A.L., Mohammad, N., Babak, T., Siu, H., Hughes, T.R., Morris, Q.D., Frey, B. J., and Blencowe, B. J. (2004). Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. Mol Cell 16: 929-941. PMID: 15610736
Reviews and Book Chapters
Calarco, J.A.*, Saltzman, A.L.*, Ip, J.Y., and Blencowe, B.J. (2007). Technologies for the global discovery and analysis of alternative splicing. In Alternative Splicing in the Postgenomic Era, B.J. Blencowe, and B.R. Graveley, eds. (Austin, Landes Biosciences), pp. 64-84. PMID: 18380341
Hughes, T.R., Hiley, S.L., Saltzman, A.L., Babak, T., and Blencowe, B.J. (2006). Microarray analysis of RNA processing and modification. Methods Enzymol 410: 300-316. PMID: 16938557