Histone modifications provide a mechanism for regulating the diverse structural and functional features of chromatin, including control of gene regulation and maintenance of genomic integrity. Histone modifications play important roles in cell growth and survival, differentiation, embryonic development, and their related pathologies, including oncogenic transformation. Recently, we have made the exciting discovery of the first bona fide histone demethylase LSD1 (Lysine-Specific Demethylase 1). The identification of LSD1 as an H3-lysine 4 (H3-K4) specific histone demethylase revealed the reversible nature of histone methylation. It not only settled the longstanding debate regarding histone demethylation, but also represented a major advance in our understanding of epigenetic gene regulation. LSD1 has also been found in a variety of multi-subunit complexes involved in gene regulation. It is a coregulator for androgen receptor mediated gene regulation, suggesting that histone demethylation may serve as a fundamental mechanism for hormone action at the transcription level. The focus of our research is on the regulation of histone demethylase(s) and the biological consequences of histone demethylation in nuclear receptor mediated gene regulation. These are fundamental events in hormone-dependent biological processes and are important for stem cell differentiation and embryonic development. Using LSD1 as the first molecular model, we aim to define histone demethylation as a novel, yet widespread regulatory mechanism for steroid hormone receptor (e.g. androgen, glucocorticoid, and thyroid receptors) action on target genes. Data derived from these studies will contribute to the rapidly advancing and groundbreaking field of epigenetics. The findings from these studies will provide significant insights into the mechanisms underlying histone demethylation as it relates to nuclear hormone receptor mediated gene regulation. They will also greatly contribute to our understanding of hormone physiology and a variety of human pathologies, including tumorigenesis and developmental anomalies.Histone modifications provide a mechanism for regulating the diverse structural and functional features of chromatin, including control of gene regulation and maintenance of genomic integrity. Histone modifications play important roles in cell growth and survival, differentiation, embryonic development, and their related pathologies, including oncogenic transformation. The focus of our research is on the regulation of histone demethylase(s) and the biological consequences of histone demethylation in nuclear receptor mediated gene regulation. These are fundamental events in hormone-dependent biological processes and are important for stem cell differentiation and embryonic development.
