Ruiz-Romero, M. | Search bioRxiv

bioRxiv2020

Dynamics of gene expression and chromatin marking during cell state transition

We have monitored the transcriptomic and epigenomic status of cells at twelve time-points during the transdifferentiation of human pre-B cells into macrophages. Using this data, we have investigated some fundamental questions regarding the role of chromatin in gene expression. We have found that, over time, genes are characterized by a limited number of chromatin states (combinations of histone modifications), and that, consistently, chromatin changes over genes tend to occur in a coordinated manner. We have observed strong association between these changes and gene expression only at the time of initial gene activation. Activation is preceded by H3K4me1 and H3K4me2, and followed in a precise order by most other histone modifications. Further changes in gene expression, comparable or even stronger than those at initial activation, occur without associated changes in histone modifications. The data generated here constitutes, thus, a unique resource to investigate transcriptomic and epigenomic dynamics during a differentiation process.

genomics↗

bioRxiv2019

bsAS, an antisense long non-coding RNA, controls cell fate through regulation of blistered/DSRF isoform expression

SummaryNatural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data in eye-antenna, leg, and wing at third instar larvae. Among the candidate NATs, we found bsAS, antisense to bs/DSRF, a gene involved in wing development and neural processes. Through the analysis of the RNA-Seq data, we found that these two different functions are carried out by the two different protein isoforms encoded in the bs gene. We also found that the usage of these isoforms is regulated by bsAS. This regulation is essential for the correct determination of cell fate during Drosophila development, as bsAS knockouts show highly aberrant phenotypes. bs regulation by bsAS is mediated by the specific physical interaction of the bsAS promoter with the promoters of bs, and it likely involves a mechanism, where expression of bsAS leads to the collision of RNA polymerases acting in opposite directions, preventing the elongation of the longer isoforms of bs, the ones carrying the neural related functions. Evolutionary analysis suggests that the bsAS NAT emerged simultaneously to the long-short isoform structure of bs, preceding the emergence of wings in insects, and maybe related to regulation of neural differentiation.

molecular biology↗