Life Sciences Commons^™

Linker Histone H1 And H3k56 Acetylation Are Antagonistic Regulators Of Nucleosome Dynamics, Morgan Bernier, Yi Luo, Kingsley C. Nwokelo, Michelle Goodwin, Sarah J. Dreher, Pei Zhang, Mark R. Parthun, Yvonne N. Fondufe-Mittendorf, Jennifer J. Ottesen, Michael G. Poirier

Molecular and Cellular Biochemistry Faculty Publications

H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF …

Genome-Wide Profiling Of Parp1 Reveals An Interplay With Gene Regulatory Regions And Dna Methylation, Narasimharao Nalabothula, Taha Al-Jumaily, Abdallah M. Eteleeb, Robert M. Flight, Shao Xiaorong, Hunter Moseley, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme involved in DNA repair, chromatin remodeling and gene expression. PARP1 interactions with chromatin architectural multi-protein complexes (i.e. nucleosomes) alter chromatin structure resulting in changes in gene expression. Chromatin structure impacts gene regulatory processes including transcription, splicing, DNA repair, replication and recombination. It is important to delineate whether PARP1 randomly associates with nucleosomes or is present at specific nucleosome regions throughout the cell genome. We performed genome-wide association studies in breast cancer cell lines to address these questions. Our studies show that PARP1 associates with epigenetic regulatory elements genome-wide, such as active histone …

Inorganic Arsenic-Induced Cellular Transformation Is Coupled With Genome Wide Changes In Chromatin Structure, Transcriptome And Splicing Patterns, Caitlyn Riedmann, Ye Ma, Manana Melikishvili, Steven Grason Godfrey, Zhuo Zhang, Kuey-Chu Chen, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with a higher than normal risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes resulting from arsenic exposure and withdrawal.

RESULTS: In these studies, we sought to understand the molecular mechanisms behind the biological changes induced by arsenic exposure. A comprehensive global approach was employed to determine genome-wide changes to chromatin structure, transcriptome patterns and splicing patterns in …