Histone Interacting Proteins in the Regulation of Chromatin Dynamics and Transcription Regulation: Implications in Disease and Differentiation
Tapas Kundu, Professor, JNCASR
Non-histone chromatin-associated proteins dynamically interact with nucleosomal histones as well as DNA and modulate chromatin fluidity, thereby regulating the underlying gene expression. We found that, multifunctional nucleolar protein NPM1 is a histone chaperone and a potent regulator of RNA pol II driven transcription which presumably is critical for both physiological and pathophysiological (oral cancer) state of human cell. Our laboratory has also discovered that highly abundant human transcriptional positive coactivator PC4 is a histone interacting bonafide component of chromatin, involved in the genome compaction and organization. Silencing of PC4 dramatically alter the genome stability and thus gene expression which is critical for breast cancer manifestation. Brain specific knocking down of PC4 leads to significant defects in neurogenesis and also memory extinction.
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