Roza Berhanu Lemma

• Rodriguez- Castañeda, Fernando; Lemma, Roza Berhanu; Cuervo Torre, Ignacio; Bengtsen, Mads; Moen, Lisa Marie; Ledsaak, Marit; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2018). The SUMO protease SENP1 and the chromatin remodeller CHD3 interact and jointly affect chromatin accessibility and gene expression. Journal of Biological Chemistry.  ISSN 0021-9258.  293(40), s 15439- 15454 . doi: 10.1074/jbc.RA118.002844 Vis sammendrag

  The small ubiquitin-like modifier (SUMO) post-translationally modifies lysine residues of transcription factors and co-regulators and thereby contributes to an important layer of control of the activities of these transcriptional regulators. Likewise, deSUMOylation of these factors by the sentrin-specific proteases (SENPs) also plays a role in gene regulation, but whether SENPs functionally interact with other regulatory factors that control gene expression is unclear. In the present work, we focused on SENP1, specifically, on its role in activation of gene expression investigated through analysis of the SENP1 interactome, which revealed that SENP1 physically interacts with the chromatin remodeler chromodomain helicase DNA-binding protein 3 (CHD3). Using several additional methods, including GST pull-down and co-immunoprecipitation assays, we validated and mapped this interaction, and using CRISPR-Cas9–generated CHD3- and SENP1-KO cells (in the haploid HAP1 cell line), we investigated whether these two proteins are functionally linked in regulating chromatin remodeling and gene expression. Genome-wide ATAC-Seq analysis of the CHD3- and SENP1-KO cells revealed a large degree of overlap in differential chromatin openness between these two mutant cell lines. Moreover, motif analysis and comparison with ChIP-Seq profiles in K562 cells pointed to an association of CHD3 and SENP1 with CCCTC-binding factor (CTCF) and SUMOylated chromatin–associated factors. Lastly, genome-wide RNA-Seq also indicated that these two proteins co-regulate the expression of several genes. We propose that the functional link between chromatin remodeling by CHD3 and deSUMOylation by SENP1 uncovered here provides another level of control of gene expression.

• Fuglerud, Bettina Maria; Lemma, Roza Berhanu; Wanichawan, Pimthanya; Sundaram, Arvind; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2017). A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function. Nucleic Acids Research.  ISSN 0305-1048.  45(13), s 7681- 7696 . doi: 10.1093/nar/gkx364

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