ACTIVATORS AND REPRESSORS OF TRANSCRIPTION: USING BIOINFORMATICS APPROACHES TO ANALYZE AND GROUP HUMAN TRANSCRIPTION FACTORS by Ala Savitskaya A Thesis Submitted to the Faculty of The Charles E. Schmidt College of Science in Partial Fulfillment of the Requirements for the Degree of Master of Science Florida Atlantic University Boca Raton, Florida May 2010 ACKNOWLEDGEMENTS The author wishes to express her thanks to her advisor Dr. Kasirajan Ayyanathan for his continued support and the time and effort put into this project, and to her committee members Dr. Zhongwei Li and Dr. Xing-Hai Zhang for their time, knowledge, insight, and ideas on how to improve further her research. The author would also like to thank all members of Dr. Ayyanathan laboratory as well as the technicians at Florida Atlantic University for their assistance and support. Special thanks go to the former undergraduate student of Dr. Ayyanathan laboratory, Leo Wolfe, for sharing his Information Technology knowledge and to the author’s family for their support and encouragement. iii ABSTRACT Author: Ala Savitskaya Title: Activators and Repressors of Transcription: Using Bioinformatics Approaches to Analyze and Group Human Transcription Factors Institution: Florida Atlantic University Thesis Advisor: Dr. Kasirajan Ayyanathan Degree: Master of Science Year: 2010 Transcription factors are macromolecules that are involved in transcriptional regulation by interacting with specific DNA regions, and they can cause activation or silencing of their target genes. Gene regulation by transcriptional control explains different biological processes such as development, function, and disease. Even though transcriptional control has been of great interest for molecular biology, much still remains unknown. This study was designed to generate the most current list of human transcription factor genes. Unique entries of transcription factor genes were collected and entered into Microsoft Office 2007 Access Database along with information about each gene. Microsoft Office 2007 Access tools were used to analyze and group collected entries according to different properties such as activator or repressor record, or presence of certain protein domains. Furthermore, protein sequence alignments of members of iv different groups were performed, and phylogenetic trees were used to analyze relationship between different members of each group. This work contributes to the existing knowledge of transcriptional regulation in human. v ACTIVATORS AND REPRESSORS OF TRANSCRIPTION: USING BIOINFORMATICS APPROACHES TO ANALYZE AND GROUP HUMAN TRANSCRIPTION FACTORS List of Tables................................................................................................................ vii List of Figures ............................................................................................................. viii Introduction ..................................................................................................................... 1 Study Design and Data Analysis ...................................................................................... 4 Study Design........................................................................................................ 4 A Database Compilation of All Human Transcription Factors .............................. 5 Major DNA-binding Domains .............................................................................. 6 Other DNA-binding Domains ............................................................................ 12 DNA-binding Domains that have not Previously been Discussed in Human TF Studies ............................................................................................................... 21 Discussion ..................................................................................................................... 26 Summary ........................................................................................................... 26 Limitations ......................................................................................................... 26 Future Studies .................................................................................................... 27 Tables and Figures ......................................................................................................... 28 Works Cited ................................................................................................................ 118 vi LIST OF TABLES Table 1: ZF-C2H2 KRAB Transcription Factors ............................................................. 28 Table 2: ZF-C2H2 SCAN Transcription Factors ............................................................. 34 Table 3: ZF-C2H2 BTB Transcription Factors ................................................................ 35 Table 4: ZF-C2H2 without KRAB, SCAN, BTB Domains .............................................. 36 Table 5: Homeobox Transcription Factors ..................................................................... 42 Table 6: HLH Transcription Factors .............................................................................. 47 Table 7: bZip Transcription Factors ............................................................................... 50 Table 8: ZF-C4 Transcription Factors ........................................................................... 52 Table 9: Forkhead Transcription Factors ........................................................................ 53 Table 10: p53-like Transcription Factors........................................................................ 54 Table 11: HMG Transcription Factors ........................................................................... 56 Table 12: ETS(a) and TIG(b) Transcription Factors ....................................................... 57 Table 13: POU(a), SAND(b), and IRF(c) Transcription Factors ..................................... 58 Table 14: GATA(a), DM(b), HSF(c), and CP2(d) Transcription Factors ........................ 59 Table 15: RFX(a) and AP2(b) Transcription Factors ...................................................... 60 Table 16: MYB DNA-Binding Transcription Factors ..................................................... 61 Table 17: MH1(a), PAX(b), and ARID(c) Transcription Factors .................................... 62 Table 18: CUT Transcription Factors ............................................................................. 63 vii LIST OF FIGURES Figure 1: Transcription Factor Genes (All) .................................................................... 64 Figure 2: Transcription Factor Genes (Activators) ......................................................... 70 Figure 3: Transcription Factor Genes (Repressors) ........................................................ 72 Figure 4: Transcription Factor Genes (Activators and Repressors) ................................. 74 Figure 5: Phylogenetic Relationship Between Genes with KRAB Domain ..................... 75 Figure 6: Phylogenetic Relationship Between Genes with SCAN Domain ..................... 81 Figure 7: Phylogenetic Relationship Between Genes with BTB Domain ........................ 82 Figure 8: Phylogenetic Relationship Between Genes with Zinc Finger C2H2 domain but without KRAB, SCAN, or BTB Domains ...................................................... 83 Figure 9: Phylogenetic Relationship Between Genes with Homeobox Domain .............. 89 Figure 10: Phylogenetic Relationship Between Genes with HLH Domain...................... 94 Figure 11: Phylogenetic Relationship Between Genes with bZip Domain ...................... 96 Figure 12: Phylogenetic Relationship Between Genes with ZF C4 Domain.................... 97 Figure 13: Phylogenetic Relationship Between Genes with Forkhead Domain ............... 98 Figure 14: Phylogenetic Relationship Between p53-like Genes ...................................... 99 Figure 15: Phylogenetic Relationship Between Genes with HMG Domain .................. 100 Figure 16: Phylogenetic Relationship Between Genes with ETS(a) and TIG(b) Domains ..................................................................................................... 101 viii Figure 17: Phylogenetic Relationship Between Genes with POU(a), SAND(b), and IRF(c) Domains .......................................................................................... 102 Figure 18: Phylogenetic Relationship Between Genes with GATA(a), DM(b), and HSF(c) Domains ...................................................................................................... 103 Figure 19: Phylogenetic Relationship Between Genes with CP2(a), RFX(b), and AP2(c) Domains ...................................................................................................... 104 Figure 20: Phylogenetic Relationship Between Genes with MYB(a) and MH1(b) Domains ..................................................................................................... 105 Figure 21: Phylogenetic Relationship Between Genes with PAX(a), AIRD(b), and CUT(c) Domains ........................................................................................ 106 Figure 22: Phylogenetic Relationship Among Genes with Documented Transcriptional Activation Function ..................................................................................... 107 Figure 23: Phylogenetic Relationship Among Genes with Documented Transcriptional Repression Function .................................................................................... 112