In eukaryotic cells, long DNA molecules are wrapped around specialized proteins called histones, forming a compact structure known as chromatin. At its most basic level, chromatin is arranged into repeating units called nucleosomes. Each nucleosome consists of approximately 147 base pairs of DNA wrapped around a core of four histone proteins (H2A, H2B, H3, and H4), with two copies of each. This structure helps condense DNA while still allowing controlled access for crucial cellular processes such as gene expression and replication. In more complex organisms, such as humans, an additional protein known as a linker histone (H1) binds to the DNA between nucleosomes, forming a structure called a chromatosome (H1 + nucleosome). Linker histones play a vital role in further compacting chromatin into higher-order structures, ensuring that DNA remains properly organized and regulated. Humans possess 11 different variants of linker histones, each potentially influencing chromatin structure in distinct ways. Beyond histones, chromatin structure is also influenced by various other proteins. These include histone chaperones, which aid in nucleosome assembly and disassembly; chromatin remodeling enzymes, which reposition nucleosomes to expose or conceal specific DNA regions; and histone modification enzymes, which chemically modify histones to regulate DNA accessibility. Additionally, transcription factors and kinetochore proteins are essential for gene regulation and chromosome organization. Notably, mutations in histones and transcription factors have been associated with cancer.

To investigate these complex processes and contribute to advancements in cancer therapeutics, we utilize a range of cutting-edge scientific techniques, including nuclear magnetic resonance (NMR), X-ray crystallography, cryo-electron microscopy (Cryo-EM), isothermal titration calorimetry (ITC), and Förster resonance energy transfer (FRET). Our current research focuses on the following molecular interactions, including (i) How histones interact with their chaperones to maintain chromatin stability; (ii) How pioneer transcription factors recognize their native nucleosome targets to regulate chromatin structure and gene activity; (iii) How linker histones together with heterochromatin protein 1 (HP1) contribute to chromatin compaction and gene suppression. By exploring these fundamental mechanisms, we aim to enhance our understanding of DNA organization within cells, with significant implications for gene regulation, cellular development, and disease processes, including cancer.