Aiturgan Zheenbekova



MMRES student at CRG and ICFO
Class 2019-2020

After MMRES:

PhD at Max Planck Institute for Biophysical Chemistry, Germany

Nascent RNA experiments reveal the role of ASH2 in co-transcriptional splicing


Chromatin modifications are epigenetic “codes” that are found to govern gene expression. Epigenetics plays an essential role in various diseases including cancer and degenerative diseases. Thus, offering insight into the mechanisms by which chromatin regulates gene expression and RNA processing is crucial. Histone H3 trimethylation at lysine 4 (H3K4me3) is a wellknown mark related to transcriptional activation. For the deposition of this mark, the trithorax group protein ASH2, cofactor of histone methyltransferase, is required. The fact that RNA Polymerase II (Pol II) phosphorylated in Ser5 is reduced in ash2 mutants led us to hypothesize that absence of ASH2 and H3K4me3 causes a fast escape of Pol II from stalling and this escape may result in lower co-transcriptional splicing efficiencies. In order to test this hypothesis, we carried out nascent RNA sequencing experiments (NUN-seq) along with polyA RNA-seq on ash2 and slow polymerase mutants as well as in wild type (WT) flies. Intron Retention (IR) analyses showed that the efficiency of co-transcriptional splicing was lower in ash2 mutants compared to WT and slow polymerase flies.

Major project supervisor

Roderic Guigó

Minor project supervisor

María García-Parajo