Biological phenomena Transcription, Replication, Repair, Recombination Development, Reprogramming, Aging, Tumorigenesis DNA methylation Histon modification Epigenetics Chromatin 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 11 Histon modification
The tails are required for transcription H3 /H3 tail H4 H2A H2B Luger et al. Nature 1997 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 12 H3 H4 H2A H2B H3 ‘tail’ The tails are required for transcription Luger et al., Nature 1997
Gene Activation in Chromatin Adaptor Histone Activator recruitment HAT)Acetyltransferase of histone modifiers Ac Nucleosomes altered Transcription and transcription RNA Pol ll m屡 TATA 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 13 Gene Activation in Chromatin TATA Act HAT Ac Histone Activator recruitment Acetyltransferase of histone modifiers Adaptor TATA TBP RNA Pol II Transcription Nucleosomes altered and transcription Act
Histone Deacetylation correlates with gene repression HML O MAT HMR a Inactive Active Anactive Sir1( Sir 3 Sir2 Trancriptional silencing in yeast is associated with reduced nucleosome acetylation Mirian Braunstein, Alan B. Rose. Scott G. Holmes, C. David Allis and James r Broach geneS DEVELOPMENT 7: 592-604C 1993 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 14 Histone Deacetylation correlates with gene repression HML α MAT HMR a Inactive Active Inactive Sir1 Sir3 Sir2 Trancriptional silencing in yeast is associated with reduced nucleosome acetylation Mirian Braunstein, Alan B. Rose, Scott G. Holmes, C. David Allis and James R. Broach. GENES & DEVELOPMENT 7:592-604 © 1993
An example of transcriptional activation in the context of chromatin The promoter is assembled into a nucleosomal 的的的的的的AM structure that is transcriptionally inactive. Interaction of a sequence-specific DNA binding TATA protein(A)recruits a chromatin-remodeling SWUSNF complex(SW/SNF), which results in stabilized binding of protein a through an ATP-dependent perturbation of nucleosomal structure. In some promoters, a partial initiation complex (TFIIB, TBP)may also be bound at this stage. Transcription OF TATA After remodeling, a histone acetyltransferase complex( HAT) is targeted to the promote. o,nal where it acety lates nucleosomes (in green)and SWUSNE facilitates the binding of a second transcription TFIID RNAPTT activator(B). A complete initiation complex TFIID, RNAP I)may be formed at this stage on Transcription OF some promoters Protein b engages a mediator/coactivator TATA complex(Mediator)and induces a particular structural conformation, which imparts specificity to its interaction with components of the initiation complex. This results in RNAP ll release and activated transcription Transcription ON Chaoan Wu. Fuaannrunv TATA
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 15 An example of transcriptional activation in the context of chromatin The promoter is assembled into a nucleosomal structure that is transcriptionally inactive. Interaction of a sequence-specific DNA binding protein (A) recruits a chromatin-remodeling complex (SWI/SNF), which results in stabilized binding of protein A through an ATP-dependent perturbation of nucleosomal structure. In some promoters, a partial initiation complex (TFIIB, TBP) may also be bound at this stage. After remodeling, a histone acetyltransferase complex (HAT) is targeted to the promoter, where it acetylates nucleosomes (in green) and facilitates the binding of a second transcriptional activator (B). A complete initiation complex (TFIID, RNAP II) may be formed at this stage on some promoters. Protein B engages a mediator/coactivator complex (Mediator) and induces a particular structural conformation, which imparts specificity to its interaction with components of the initiation complex. This results in RNAP II release and activated transcription