Regulation of differentiation-specific genes by the Drosophila RB, E2F, and Myb-interacting proteins complex (dREAM)

Abstract

OF THE DISS ERTATION ii ACKNOWLEDGEMENT iv TABLE OF CONTENTS v LIST OF FIGURES viii LIST OF TABLES x CHAPTER I Introduction 1. E2F/RB family of proteins are transcription factors that regulate the cell cycle 2 2. Members of E2F/RB system 4 A. E2F proteins in mammalian systems 4 (i) Activator E2F proteins (E2F1-3) 4 (ii) Repressive E2F proteins (E2F4-5) 7 (ii) Repressive E2F proteins with distinct repression mechanisms (E2F6, 7, 8) 7 B. DP proteins are required for DNA b inding of E2Fs 8 C. RB family proteins regulate E2Fs. 9 D. Homologs of E2F and RB in worms and flies 12 3. Cell cycle regulation of E2F and RB 16 A. CDK mediated phosphorylation of RB family o f proteins is important for the G1/S transition ....... 16 B. CDK inhib itors regulate CDK activity, and thus E2F/RB functions 18 4. Mechanisms of transcriptional regulation by RB/E2F family members 21 A. E2F proteins activate transcription 21 B. E2F/RB proteins repress transcription 22 (i) Passive repression 22 (ii) Active repression by chromatin remodeling 22 5. Biological Functions of E2F/RB family proteins 28 A. Functions of E2F/RB 28 B. E2F/RB proteins control the cell cycle 28 (i) E2F/RB regulates the cell cycle at the G1/S transition 28 (ii) E2F/RB regulates the cell cycle beyond G1/S transition 30 C. E2F/RB proteins regulate apoptosis 31 D. Regulation of d ifferentiation and developmental p rocesses 35 6. Cell cycle-independent functions of E2F and RB 39 A. Regulation of d ifferentiation specific genes 39 B. Regulation of Apoptotic genes 43 7. dREAM complex dependent repression 44