Doctor of Philosophy, Universidad De Barcelona (2018)
Master of Science, Universidad De Barcelona (2012)
Licenciatura, Unlisted School (2011)
Joanna Wysocka, Postdoctoral Faculty Sponsor
JMJD3 intrinsically disordered region links the 3D-genome structure to TGFbeta-dependent transcription activation.
2022; 13 (1): 3263
Enhancers are key regulatory elements that govern gene expression programs in response to developmental signals. However, how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter remains unclear. To address this question, we exploited our previously characterized TGFbeta-response model, the neural stem cells, focusing on a ~374kb locus where enhancers abound. Our 4C-seq experiments reveal that the TGFbeta pathway drives the assembly of an enhancer-cluster and precise gene activation. We discover that the TGFbeta pathway coactivator JMJD3 is essential to maintain these structures. Using live-cell imaging techniques, we demonstrate that an intrinsically disordered region contained in JMJD3 is involved in the formation of phase-separated biomolecular condensates, which are found in the enhancer-cluster. Overall, in this work we uncover novelfunctions for the coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin and the TGFbeta-driven response during mammalian neurogenesis.
View details for DOI 10.1038/s41467-022-30614-y
View details for PubMedID 35672304
Roles of transposable elements in the regulation of mammalian transcription.
Nature reviews. Molecular cell biology
Transposable elements (TEs) comprise about half of the mammalian genome. TEs often contain sequences capable of recruiting the host transcription machinery, which they use to express their own products and promote transposition. However, the regulatory sequences carried by TEs may affect host transcription long after the TEs have lost the ability to transpose. Recent advances in genome analysis and engineering have facilitated systematic interrogation of the regulatory activities of TEs. In this Review, we discuss diverse mechanisms by which TEs contribute to transcription regulation. Notably, TEs can donate enhancer and promoter sequences that influence the expression of host genes, modify 3D chromatin architecture and give rise to novel regulatory genes, including non-coding RNAs and transcription factors. We discuss how TEs spur regulatory evolution and facilitate the emergence of genetic novelties in mammalian physiology and development. By virtue of their repetitive and interspersed nature, TEs offer unique opportunities to dissect the effects of mutation and genomic context on the function and evolution of cis-regulatory elements. We argue that TE-centric studies hold the key to unlocking general principles of transcription regulation and evolution.
View details for DOI 10.1038/s41580-022-00457-y
View details for PubMedID 35228718