方向(目標)一:決定組蛋白去乙醯化對於 ZFP42 轉錄抑制功能的影響
方向(目標)二:決定組蛋白甲基化對於 ZFP42 轉錄抑制功能的影響
方向(目標)三:決定聚腺核甘二磷酸聚合修飾作用對於 ZFP42 轉錄抑制功能的
影響
ZFP42 is a zinc-finger protein of the Krüpple-like factor (KLF) family known as a markerfor the embryonic lineage during development. However, the function of ZFP42 is almost
completely unknown. Previously we demonstrated that ZFP42 is a transcriptional repressor.We now have preliminary results suggesting that ZFP42 represses transcription from the immunoglobulin κ light chain enhancer and interacts with histone deacetylases, a histonemethyltransferase, and a poly(ADP-ribose) polymerase. It has been shown that histonedeacetylation, histone methylation of specific lysine residues, and poly(ADP-ribosyl)ation
status of histones as well as transcription factors all contribute to the establishment of a closedchromatin structure and hence transcriptional repression. In this proposed study, we would
like to explore the mechanism of transcription repression of ZFP42 from a molecular level. I hypothesize that ZFP42 represses transcription through interacting with chromatin-modifying
proteins, thereby creating a local environment favorable for repression. The following three aims will be executed to test this hypothesis:
Aim 1. to determine the functional relationship between histone deacetylation and ZFP42-mediated transcriptional repression
Aim 2. to determine the functional relationship between histone methylation and ZFP42-mediated transcriptional repression
Aim 3. to determine the functional relationship between poly(ADP-ribosyl)ation and ZFP42-mediated transcriptional repression