Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/121843
Title: CELL CYCLE REGULATORY MECHANISMS IN SKELETAL MUSCLE CELLS
Authors: MANIGHATTA BHEEMA RAO VINAY KUMAR
Keywords: G9a, Myoblast cell cycle exit, Proliferation
Issue Date: 16-Jul-2015
Source: MANIGHATTA BHEEMA RAO VINAY KUMAR (2015-07-16). CELL CYCLE REGULATORY MECHANISMS IN SKELETAL MUSCLE CELLS. ScholarBank@NUS Repository.
Abstract: IN MUSCLE CELLS, PROLIFERATION AND DIFFERENTIATION ARE MUTUALLY EXCLUSIVE EVENTS THAT ARE CONTROLLED BY THE TRANSCRIPTION FACTOR MYOD. DURING DIFFERENTIATION, MYOD-DEPENDENT CELL CYCLE EXIT IS MEDIATED BY P21CIP1/WAF1 AND RB1 THAT IS NECESSARY FOR CELLS TO DIFFERENTIATE. G9A, A LYSINE METHYLTRANSFERASE INHIBITS MYOGENIC DIFFERENTIATION. TO IDENTIFY G9A TARGETS, MICROARRAY ANALYSIS WAS PERFORMED. SEVERAL GENES INVOLVED IN CELL CYCLE CONTROL WERE DE-REGULATED IN G9A KNOCKDOWN CELLS. IN GAIN-OF-FUNCTION AND LOSS-OF-FUNCTION ASSAYS, G9A WAS FOUND TO PROMOTE PROLIFERATION OF CELLS AND INHIBIT CELL CYCLE EXIT. G9A-MEDIATED INHIBITION OF DIFFERENTIATION WAS RESCUED BY RE-EXPRESSION OF P21CIP1/WAF1 AND RB1. INTERESTINGLY, G9A OCCUPANCY CORRELATED WITH REPRESSIVE HISTONE METHYLATION MARKS ON P21CIP1/WAF1 AND RB1 PROMOTERS, BUT NOT ON E2F1-TARGET GENES. OUR DATA SUPPORT A MODEL IN WHICH G9A BOTH PROMOTES PROLIFERATION AND PREVENTS CELL CYCLE EXIT OF MUSCLE CELLS TO BLOCK DIFFERENTIATION. THESE
URI: http://scholarbank.nus.edu.sg/handle/10635/121843
Appears in Collections:Ph.D Theses (Open)

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