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Full-Text Articles in Life Sciences
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Electronic Thesis and Dissertation Repository
The retinoblastoma protein (RB) is historically known for its function in cell cycle control. However, mice carrying targeted Rb1 mutations have revealed that RB serves various non-cell cycle control roles. Notably, RB acts as a scaffold that recruits chromatin regulatory proteins, condensin II and enhancer of zeste homolog 2 (EZH2). These complexes protect the genome integrity through maintaining proper chromosome condensation, long range contacts, and transcriptionally repressive histone modification. This thesis explores the mechanistic links that regulate such RB-condensin II complex or that are leveraged upon pharmacological inhibition of the RB-EZH2 complex. First, I identified potential phosphorylation sites in the …
Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu
Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu
Biochemistry Publications
Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were …
The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak
The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak
Electronic Thesis and Dissertation Repository
This thesis investigates mechanistic links between genome integrity and the recruitment of chromatin organizing proteins to repetitive DNA sequences mediated by the retinoblastoma tumor suppressor protein (pRB). I demonstrate that a CDK-resistant interaction between the pRB C-terminus and the E2F1 coiled-coil marked box domain establishes a scaffold that facilitates recruitment of multiple chromatin-organizing proteins to repetitive sequences across the genome throughout the cell cycle. Specifically, pRB recruits the enhancer-of-zeste-homologue 2 (EZH2) histone methyltransferase to establish repressive facultative heterochromatin at repetitive sequences, and the Condensin II complex to ensure proper DNA replication and mitotic progression. To disrupt the CDK-resistant pRB-E2F1 interaction …