Identifying Novel Transcriptional and Epigenetic Features of Nuclear Lamina-associated Genes

Feinan Wu,Jie Yao

doi:10.1038/s41598-017-00176-x

Abstract

Because a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes. At the genome-wide scale, NL-association and H3K27me3 distinguishes two large gene classes with low transcriptional activities. Notably, NL-association is anti-correlated with both transcription and active histone mark levels among genes not significantly enriched with H3K9me3 or H3K27me3, suggesting that NL-association may represent a novel gene repression pathway. Interestingly, an NL gene subgroup is not significantly enriched with H3K9me3 or H3K27me3 and is transcribed at higher levels than the rest of NL genes. Furthermore, we identified distal enhancers associated with active NL genes and reported their epigenetic features.

Highlights

The mammalian genome is compacted, spatially organized and compartmentalized within the cell nucleus[1]
We found that nuclear lamina association (NLA) was anti-correlated with active histone marks among genes transcribed at the same level, indicating that active histone marks may be repressed near the nuclear lamina (NL)
We detected transcriptionally-engaged RNA polymerase II (Pol II) in gene bodies of active NL genes, indicating that active NL genes are permissive to transcriptional elongation in the gene body

Summary

Introduction

The mammalian genome is compacted, spatially organized and compartmentalized within the cell nucleus[1]. Several studies identified the connections between chromatin status, gene expression and gene localization at the nuclear periphery in mammalian cells. Association of circadian genes with the NL in human cells was dependent upon PARP1 and CTCF and preceded their transcriptional repression[11]. While these case studies are highly informative, a genome-wide analysis will enable identifying transcriptional and epigenetic features of NL-associated genes that are critical for revealing their regulation. By genome-wide clustering analysis, we found that nuclear lamina association (NLA) and H3K27me[3] are the predominant epigenetic features of two distinct classes of repressed genes. We identified NL gene subgroups that are differentially enriched with repressive histone marks and identified distal enhancers associated with active NL genes

Methods

Results

Conclusion