Talk abstracts

Talk on Monday 11:05-11:20am submitted by Mansi Arora

Chromatin Ubiquitination and Transcriptional Memory

Mansi S. Arora (Biomedical Informatics, The Ohio State University), Jie Zhang (Biomedical Informatics, The Ohio State University), Gulcin H Ozer (Biomedical Informatics, The Ohio State University), Huiwen Liu (Biomedical Informatics, The Ohio State University), Kun Huang (Biomedical Informatics, The Ohio State University), Jeffrey D, Parvin (Biomedical Informatics, The Ohio State University)

Abstract:
It is well known that combination of transcription factors and chromatin modifications regulate gene expression pertinent to a specific cell type during cell cycle interphase. This transcriptional regulatory information must be inherited during each cell division to sustain a similar gene expression pattern in progeny cells. During mitosis, the cellular and nuclear architecture undergoes global remodeling, DNA is condensed and most of the transcription program is halted. How the transcriptional information is passed on from one generation to the other is not very clear. A process called ‘gene bookmarking’ is just beginning to be understood with recent works showing retention of several transcription factors at promoter regions of their target genes during mitosis. This enables rapid reactivation of the target genes once cell division is complete. Little is known about retention of chromatin modifications through mitosis.

Our preliminary results suggest a role for chromatin ubiquitination in transcriptional memory. Histone ubiquitination has been associated with transcriptional elongation. Differing from previous results, we first show that both transcribed regions and promoters of active genes are ubiquitinated. We also show that promoter ubiquitination is not just retained through the cell cycle, but in fact increases during mitosis as compared to other cell cycle stages. This promoter ubiquitination is reduced after the cells proceed through mitosis and enter the G1 phase of cell cycle. Comparison with other histone modifications shows a significant overlap with histone H3K4 trimethylation (H3K4me3) during interphase. Promoter ubiquitination is also seen at genes that retain MLL (the enzyme responsible for H3K4me3) during mitosis.

We hypothesize that promoter ubiquitination during mitosis acts like a bookmark for transcription factors to bind to their target genes and cause their reactivation post mitosis.

Keywords: Chromatin, Ubiquitination, Transcription