Z-DNA-forming sites identified by ChIP-Seq are associated with actively transcribed regions in the human genome

Abstract

Z-DNA, a left-handed double helical DNA is structurally different from the most abundant B-DNA. Z-DNA has been known to play a significant role in transcription and genome stability but the biological meaning and positions of Z-DNA-forming sites (ZFSs) in the human genome has not been fully explored. To obtain genome-wide map of ZFSs, Zaa with two Z-DNA-binding domains was used for ChIP-Seq analysis. A total of 391 ZFSs were found and their functions were examined in vivo. A large portion of ZFSs was enriched in the promoter regions and contain sequences with high potential to form Z-DNA. Genes containing ZFSs were occupied by RNA polymerase II at the promoters and showed high levels of expression. Moreover, ZFSs were significantly related to active histone marks such as H3K4me3 and H3K9ac. The association of Z-DNA with active transcription was confirmed by the reporter assay system. Overall, our results suggest that Z-DNA formation depends on chromatin structure as well as sequence composition, and is associated with active transcription in human cells. The global information about ZFSs positioning will provide a useful resource for further understanding of DNA structure-dependent transcriptional regulation.

The Expression of CNS-Specific PPARGC1A Transcripts Is Regulated by Hypoxia and a Variable GT Repeat Polymorphism

“…In addition, the instable GT microsatellite is part of a highly predicted Z-DNA region. Sequences transiently forming Z-DNAs are non-randomly distributed, occur more frequently proximal to transcription start sites, and influence promoter activity [46][47][48]. Self-and cross-co-activation of both the RG and CNS promoters by the reference protein and CNS-specific isoforms were consistent findings in our transient transfection studies of SH-SY5Y cells.…”

“…The instable microsatellite region includes interspersed GC repeats. This region has a high potential for Z-DNA formation [45] known to frequently influence promoter activation [46][47][48]. To determine possible effects of the variable microsatellite on promoter activity, we amplified proximal CNS promoters (− 539 to + 63 bp relative to the transcription start site) differing in GT sizes, but otherwise containing identical sequences, from human subjects, cloned the fragments into reporter vectors, and transiently transfected the constructs into SH-SY5Y cells.…”

FACT is a sensor of DNA torsional stress in eukaryotic cells

“…Possibility of Z-DNA transition was also demonstrated for some genomic regions such as promoter zones with nucleosome removed by RNA polymerase or chromatin remodeling factors (1,87–89). Treatment of cells with CBL0137 provides the necessary conditions for Z-DNA transition, i.e.…”

Dynamic DNA structure states interact with the RNA editing enzyme ADAR1 to modulate fear extinction memory

“…The idea that ADAR1 could interact with DNA structure dates back to original observations made by Rich and colleagues who suggested that the Z-alpha domain of ADAR1 recognizes an alternative left-handed DNA structure 12,13,34 . Over the years, a very strong case has been made for the existence of Z-DNA and its role in many biological processes, particularly transcriptional regulation [37][38][39][40] . Specifically, it has been reported that Z-DNA is related to both transcriptional activation 41,42 and inhibition 43,44 .…”

“…Specifically, it has been reported that Z-DNA is related to both transcriptional activation 41,42 and inhibition 43,44 . Mechanistically, this change in structure is thought to be coupled to transcription by the recruitment of transcription factors, such as PolII, for enhancement, or the direct blockade of the transcriptional machinery leading to PollI stalling during inhibition 37,39,[45][46][47] .…”