Gregory Dressler Laboratory

Home About Greg Lab Personnel Publications Research Contact Information
  1. Home
  2. Mechanisms of Gene Regulation and Chromatin Remodeling
     

Mechanisms of Gene Regulation and Chromatin Remodeling

This project entails elements of other projects described here but focuses on more basic mechanisms of how transcription factors that specify cell lineages and tissues can alter the chromatin at target loci such that epigenetic information is passed on to all progeny cells within the lineage. Again our model protein is the Pax2 transcription factor. We exam how Pax2 is regulated in vivo and in vitro. Using both transgenic mice and novel protein purification methods, we have shown that early activation of the Pax2 intermediate mesoderm specific enhancer requires binding of the chromatin remodeling protein YY1

 

Fig-6.gif

 

Figure 6 Isolation of the YY1 protein using a combination of biochemical purification, DNA affinity chromatography, and mass spectrometry.

 

Fig-7 lg.jpg

 

Figure 7 Analysis of the Pax2 promoter and enhancer sequences in transgenic mice using EGFP as a reporter system. Various deletion constructs point to an essential role for the YY1 site in regulating Pax2 expression

 

One a related note we are studying the interactions of Pax2 with the cellular transcription machinery. Using biochemical approaches, we have identified a Pax2 interacting protein called PTIP that is an essential factor for early development. PTIP interacts with multiple cellular proteins that are involved in chromatin remodeling, DNA damage repair and cell cycle control. We have used protein purification methods and mass spectrometry to identify novel proteins within the Pax2/PTIP complex. Some of these proteins are involved in the modification of Histones, suggesting a link between cell lineage specification and the formation of chromatin domains within specific Pax2 target loci. We are using both classical differential screening methods and modern micro array approaches to identify genes regulated by Pax2. How the chromatin structure of such target genes is affected by the Pax2 PTIP complex will be investigated.