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Unraveling the Half and Full Site Sequence Specificity of the Saccharomyces cerevisiae Pdr1p and Pdr3p Transcription Factors
Unraveling the Half and Full Site Sequence Specificity of the Saccharomyces cerevisiae Pdr...
Unraveling the Half and Full Site Sequence Specificity of the Saccharomyces cerevisiae Pdr1p and Pdr3p Transcription Factors

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자료유형  
 학위논문 서양
최종처리일시  
20250211150918
ISBN  
9798381976625
DDC  
574.191
저자명  
Buechel, Evan R.
서명/저자  
Unraveling the Half and Full Site Sequence Specificity of the Saccharomyces cerevisiae Pdr1p and Pdr3p Transcription Factors
발행사항  
[Sl] : Northwestern University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
190 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-10, Section: B.
주기사항  
Advisor: Pinkett, Heather.
학위논문주기  
Thesis (Ph.D.)--Northwestern University, 2024.
초록/해제  
요약The pleiotropic drug resistance (PDR) network is an important regulatory system in Saccharomyces cerevisiae involved in the transport of various toxins and drugs out of the cell. The zinc cluster transcription factors Pdr1p and Pdr3p, key regulators of this network, bind to specific sequences called PDREs within the promoter region of the PDR genes to control expression. However, the exact mechanisms underlying the differences in the regulons of these proteins remain unclear. The focus of this dissertation is on the role of PDRE binding site sequence variation on DNA binding and transcriptional activity of Pdr1p and Pdr3p. A combination of genomic occupancy profiling (CUT&RUN), binding assays and transcription studies were employed to characterize the differences in sequence specificity between the two transcription factors. Distinct preferences for core PDRE sequences and the flanking sequences were revealed for both proteins. While flanking sequences moderately alter DNA binding affinity, they significantly impact Pdr1p/Pdr3p transcriptional activity. Moreover, although Pdr1p and Pdr3p are known to dimerize on PDRE sites, they also have the capacity to bind half sites with high affinity. Transcriptional assays reveal that like PDRE flanking sequences, these half sites appear to modulate transcription from adjacent PDREs. These studies provide insight on how sequence variation within PDREs impacts the function of both Pdr1p and Pdr3p leading to differential regulation within the PDR network.
일반주제명  
Biophysics
일반주제명  
Biochemistry
일반주제명  
Genetics
키워드  
Pleiotropic drug resistance
키워드  
Saccharomyces cerevisiae
키워드  
Transcription factors
키워드  
Genomic occupancy profiling
기타저자  
Northwestern University Interdepartmental Biological Sciences (IBiS) Graduate Program
기본자료저록  
Dissertations Abstracts International. 85-10B.
전자적 위치 및 접속  
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MARC

 008250123s2024        us                              c    eng  d
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■00520250211150918
■006m          o    d                
■007cr#unu||||||||
■020    ▼a9798381976625
■035    ▼a(MiAaPQ)AAI30817862
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574.191
■1001  ▼aBuechel,  Evan  R.▼0(orcid)0000-0002-2134-2582
■24510▼aUnraveling  the  Half  and  Full  Site  Sequence  Specificity  of  the  Saccharomyces  cerevisiae  Pdr1p  and  Pdr3p  Transcription  Factors
■260    ▼a[Sl]▼bNorthwestern  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a190  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-10,  Section:  B.
■500    ▼aAdvisor:  Pinkett,  Heather.
■5021  ▼aThesis  (Ph.D.)--Northwestern  University,  2024.
■520    ▼aThe  pleiotropic  drug  resistance  (PDR)  network  is  an  important  regulatory  system  in  Saccharomyces  cerevisiae  involved  in  the  transport  of  various  toxins  and  drugs  out  of  the  cell.  The  zinc  cluster  transcription  factors  Pdr1p  and  Pdr3p,  key  regulators  of  this  network,  bind  to  specific  sequences  called  PDREs  within  the  promoter  region  of  the  PDR  genes  to  control  expression.  However,  the  exact  mechanisms  underlying  the  differences  in  the  regulons  of  these  proteins  remain  unclear.  The  focus  of  this  dissertation  is  on  the  role  of  PDRE  binding  site  sequence  variation  on  DNA  binding  and  transcriptional  activity  of  Pdr1p  and  Pdr3p.  A  combination  of  genomic  occupancy  profiling  (CUT&RUN),  binding  assays  and  transcription  studies  were  employed  to  characterize  the  differences  in  sequence  specificity  between  the  two  transcription  factors.  Distinct  preferences  for  core  PDRE  sequences  and  the  flanking  sequences  were  revealed  for  both  proteins.  While  flanking  sequences  moderately  alter  DNA  binding  affinity,  they  significantly  impact  Pdr1p/Pdr3p  transcriptional  activity.  Moreover,  although  Pdr1p  and  Pdr3p  are  known  to  dimerize  on  PDRE  sites,  they  also  have  the  capacity  to  bind  half  sites  with  high  affinity.  Transcriptional  assays  reveal  that  like  PDRE  flanking  sequences,  these  half  sites  appear  to  modulate  transcription  from  adjacent  PDREs.  These  studies  provide  insight  on  how  sequence  variation  within  PDREs  impacts  the  function  of  both  Pdr1p  and  Pdr3p  leading  to  differential  regulation  within  the  PDR  network.
■590    ▼aSchool  code:  0163.
■650  4▼aBiophysics
■650  4▼aBiochemistry
■650  4▼aGenetics
■653    ▼aPleiotropic  drug  resistance
■653    ▼aSaccharomyces  cerevisiae
■653    ▼aTranscription  factors
■653    ▼aGenomic  occupancy  profiling
■690    ▼a0786
■690    ▼a0487
■690    ▼a0369
■71020▼aNorthwestern  University▼bInterdepartmental  Biological  Sciences  (IBiS)  Graduate  Program.
■7730  ▼tDissertations  Abstracts  International▼g85-10B.
■790    ▼a0163
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160144▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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