Highly homologous mouse Cyp2a4 and Cyp2a5 genes are differentially expressed in the liver and both express long non-coding antisense RNAs

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The mammalian Cytochrome P450 (Cyp) gene superfamily encodes enzymes involved in numerous metabolic pathways and are frequently expressed in the liver. Despite the remarkably high sequence similarity of Cyp2a4 and Cyp2a5 genes and their surrounding genomic regions, they exhibit differences in expression in the adult mouse liver. For example, Cyp2a4 is highly female-biased whereas Cyp2a5 is only moderately female-biased and Cyp2a4, but not Cyp2a5, is activated in liver cancer. We hypothesized that the limited sequence differences may help us identify the basis for this differential expression. An antisense expressed sequence tag had been uniquely annotated to the Cyp2a4 gene which led us to investigate this transcript as a possible regulator of this gene. We characterized the full-length antisense transcript and also discovered a similar transcript in the Cyp2a5 gene. These transcripts are nuclear long noncoding RNAs that are expressed similarly to their sense mRNA counterparts. This includes the sex-biased and liver tumor differences seen between the Cyp2a4 and Cyp2a5 genes, but we also find that these two genes and their antisense transcripts are expressed within different zones of the liver structure. Interestingly, while the differences in sex-biased expression of the mRNAs are established 1–2 months after birth, the antisense transcripts exhibit these expression differences earlier, at 3–4 weeks after birth. By analyzing published genomic data, we have identified candidate transcription factor binding sites that could account for differences in Cyp2a4/Cyp2a5 expression. Taken together, these studies characterize the first antisense RNAs within the Cyp supergene family and identify potential transcriptional and post-transcriptional mechanisms governing different Cyp2a4 and Cyp2a5 expression patterns in mouse liver.

Original languageEnglish
Article number145162
JournalGene
Volume767
DOIs
StatePublished - Jan 30 2021

Bibliographical note

Funding Information:
We would like to thank Kate Townsend Creasy, Guofong (Shirley) Qiu and Jieyun Jiang for providing samples and advice for this work. Statistical support was provided by the Applied Statistics Lab in the Department of Statistics that is partially funded by NIH P20GM103436 .

Funding Information:
This work was supported by the National Institutes of Health grant number NIDDK - DK074816 .

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

  • Cytochrome p450
  • Gene duplication
  • Natural antisense RNA
  • Sex-biased expression
  • lncRNA

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'Highly homologous mouse Cyp2a4 and Cyp2a5 genes are differentially expressed in the liver and both express long non-coding antisense RNAs'. Together they form a unique fingerprint.

Cite this