Chromatin and cell-type specific gene expression
During metazoan development a single embryonic stem cell gives rise to many different cell-types with distinct functions and morphologies. Underlying these cell-type specific differences are distinct patterns of gene expression that are in part determined by lineage-specific transcription factors. How these transcription factors chose amongst many possible binding sites in the genome is the subject of intense study in the field of gene regulation. Eukaryotic DNA is wrapped into chromatin and recent evidence suggests that accessibility of sites to transcription factors may be determined by the presence or absence of nucleosomes.
Research in the Floer lab focuses on understanding how induction of cell-type specific genes is controlled by chromatin in mouse immune cells. In particular, we are using bone marrow derived macrophages to determine expression of pro-inflammatory genes in response to various pathogens. The lab uses a quantitative approach to analyze nucleosome occupancy at transcriptional regulatory sites of these pro-inflammatory genes. Regulation of pro-inflammatory gene expression plays an important role in the innate immune response and aberrant regulation is associated with many different diseases, including heart disease and atherosclerosis.
Recent efforts in the lab aim at investigating how accessible chromatin at pro-inflammatory genes is established during differentiation of macrophages from hematopoietic progenitors. These studies will shed light on the mechanisms that govern cell-type specific chromatin formation, and will reveal how failure to do this can lead to cancer.