Exploring chromatin modulations and modifications during transcription

Within our cells, the genetic material, DNA, is organized as chromatin via its association with histone and non-histone proteins. An important organizational component is the nucleosome, consisting of approximately 147 base pairs (bp) of DNA and two copies each of the four canonical histone proteins. Nucleosomes at promoters of active genes are marked by specific histone post-translational modifications and histone variants. These features, in conjunction with a variety of epigenetic enzymes, are thought to promote the formation and maintenance of an "open" chromatin environment that is suitable for transcription.

Recent experiments in the laboratory have examined the roles played by the human BRG1 chromatin remodeling complex and RNA Polymerase II. Our data suggest that BRG1 plays a direct positive role in chromatin accessibility, histone acetylation, RNA Polymerase II binding, and nascent RNA production by regulating nucleosome positioning and facilitating transcription factor binding to their target sites. Our experiments with RNA Polymerase II examined whether specific histone modifications depend on active transcription. The data showed that transcription initiation was not required for active histone modifications at transcription start sites(TSS) and enhancers. Rather, blocking transcription initiation increased the levels of histone acetylation and H2AZ incorporation at active TSSs. Thus, this demonstrates the complex relationships between chromatin enzymes, architecture, and active histone modifications required for regulated transcription.

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As Deputy Director of the National Institute of Environmental Health Sciences (NIEHS), Trevor K. Archer, Ph.D., works with the NIEHS and National Toxicology Program Director, Rick Woychik, Ph.D., in the overall management of the institute. He supports the formulation and implementation of strategic plans and policies that advance the NIEHS scientific mission and research goals.  Dr. Archer remains an active research scientist and has been honored as an NIH Distinguished Investigator. His research career spans more than three decades, two of which were spent in key scientific roles at NIEHS. Dr. Archer is known for expertise in cancer biology, hormone receptors, chromatin function, epigenetics, and stem cells, as well as his dedication to advancing diversity, equity, inclusion, and accessibility across the biomedical enterprise. Before appointment as deputy director, Dr. Archer was the founding chief of the NIEHS Epigenetics and Stem Cell Biology Laboratory (ESCBL) and remains an active researcher leading the Chromatin and Gene Expression Group within the ESCBL. Recent work from his laboratory explores the multiple contributions chromatin and epigenetic enzymes play in activated transcription and early development.