Genomic Regulation

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Our lab’s aim is to integrate different levels of gene expression regulation – chromatin, transcription and RNA processing – focusing on gene ends.

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Kinga Kamieniarz-Gdula, PhD DSc

Principal Investigator

Research

We want to understand the basic mechanisms of when and how transcription stops (terminates), but also how perturbed termination contributes to disease.
Premature termination, called also transcription attenuation, is particularly relevant in the pathological context. Premature termination was known to be an important regulatory mechanism in bacteria and yeast, but overlooked in humans and animals in general. We and others have recently shown that this phenomenon is a very abundant genomic event in metazoa. It has also medical implications, particularly in cancer.
Our main approaches are based on NGS (genomics and nascent transcriptomics), combined with molecular biology, biochemistry and proteomics. The lab’s experimental workhorse are mammalian cell culture models of cancer and neuronal differentiation. We use both experimental and computational approaches.

Selected publications

CLP1-dependent premature transcription termination opposes neurodegeneration. Gdula MR, Kopczyńska M, Saha U, Kamieniarz-Gdula K. Neuron. 2022 https://doi.org/10.1016/j.neuron.2022.03.012
Transcriptional Control by Premature Termination: A Forgotten Mechanism. Kamieniarz-Gdula K, Proudfoot NJ. Trends Genet. 2019 https://doi.org/10.1016/j.tig.2019.05.005
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination. Kamieniarz-Gdula K, Gdula MR, Panser K, Nojima T, Monks J, Wiśniewski JR, Riepsaame J, Brockdorff N, Pauli A, Proudfoot NJ. Mol Cell. 2019 https://doi.org/10.1016/j.molcel.2019.01.027
WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription. Volanakis A, Kamieniarz-Gdula K [joint-first & co-corresponding author], Schlackow M, Proudfoot NJ. Genes Dev. 2017 https://doi.org/10.1101/gad.303677.117
BRCA1 recruitment to transcriptional pause sites is required for R-loop–driven DNA damage repair. Hatchi E, Skourti-Stathaki K, Ventz S, Pinello L, Yen A, Kamieniarz-Gdula K, Dimitrov S, Pathania S, McKinney KM, Eaton ML, Kellis M, Hill SJ, Parmigiani G, Proudfoot NJ, Livingston DM. Mol Cell. 2015 https://doi.org/10.1016/j.molcel.2015.01.011
R-loops induce repressive chromatin marks over mammalian gene terminators. Skourti-Stathaki K, Kamieniarz-Gdula K, Proudfoot NJ. Nature. 2014 https://doi.org/10.1038/nature13787
The genomic landscape of the somatic linker histone subtypes H1.1 to H1.5 in human cells. Izzo A, Kamieniarz-Gdula K [joint-first author], Ramírez F, Noureen N, Kind J, Manke T, van Steensel B, Schneider R. Cell Rep. 2013 https://doi.org/10.1016/j.celrep.2013.05.003
Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer. Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R. Cell. 2013 https://doi.org/10.1016/j.cell.2013.01.032
A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation. Kamieniarz K, Izzo A, Dundr M, Tropberger P, Ozretic L, Kirfel J, Scheer E, Tropel P, Wisniewski JR, Tora L, Viville S, Buettner R, Schneider R. Genes Dev. 2012 https://doi.org/10.1101/gad.182014.111