Multiple Papers on Random Monoallelic Expression by RNA-seq

Monoallelic expression by RNA-seq

Monoallelic expression by RNA-seq

Nature Methods called “single-cell sequencing” as the Method of the Year for 2013. Thanks to the technology to sequence the transcriptome of single cell, we are beginning to see a slew of papers on Single Cell Transcriptomics.

Earlier this year, we saw Science paper characterizing the prevalence of “Random Monoallelic Expression” (or transcriptional burst) in multiple stages of mouse preimplantation development (blogpost on the paper).

Continuing on the theme,  multiple interesting papers on random monoallelic expression are published recently. Two back to back papers are in the current issue of Developmental Cell. Both are open access articles.

The group led by David Spector from CSHL published

The team studied the “dynamics of monoallelic expression during development through an allele-specific RNA-sequencing screen in clonal populations of hybrid mouse embryonic stem cells(ESCs) and neural progenitor cells (NPCs)”. They found that during differentiation of mouse ESCs to NPCs, there is about 6 fold increase in the number of autosomal genes with random monoallelic expression. In addition, histone modifications, not DNA methylation or nuclear organization, seem to distinguish active and inactive alleles.

The second paper from a group in France

studied the same developmental stage, but in a different F1 mice (129Sv x CAST vs B6 x CAST). Although this paper has similar conclusions as the previous one, at a first look there are lot of interesting results that differ between these two papers. For example, the random mono-allelic expression is stable across multiple cell divisions for the five genes they tested. Also, the second paper finds evidence for both DNA methylation and H3K27me3 playing a role in maintenance of the state of random monoallelic expression. May be the handful of genes they tested were all silenced by imprinting, where methylation is known to play role. Interestingly, both the paper do not seem to discuss the effect of technical artifact creating monoallelic-like expression. The Science paper found a huge technical effect on monoallelic expression.  May be I am missing something here,  got to read in detail.

The third paper was published in eLife at the end of 2013

The team studied chromatin signature the differentiates genes with mono-allelic expression. Here is the abstract of the paper.

In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. In this study, we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in 20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation.

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