After graduating in Biochemistry (Univ. Lisbon, Portugal), Miguel did a PhD at the MRC Clinical Sciences Centre in London with Prof. Ana Pombo, where he studied the spatial organisation of the genome. He then joined Prof. Wolf Reik’s group at the Babraham Institute in Cambridge to investigate mechanisms of epigenetic regulation, and in particular the role of DNA hydroxymethylation in embryonic stem cells. In 2011 he was awarded a Next Generation Fellowship from the Centre for Trophoblast Research (Univ. of Cambridge) and joined the Blizard Institute (QMUL) in October 2013 after securing a Sir Henry Dale Fellowship from the Wellcome Trust and Royal Society.
Group website: https://brancolaboratory.com
Our group is interested in the epigenetic regulation of transposable elements and its impact on genome function. Almost half of the human genome is made up of transposons, and a proportion of these remain active and mobile. Therefore, their transcription needs to be tightly controlled to prevent mutagenic events. On the other hand, transposons have helped to drive genome evolution, often contributing with gene regulatory elements, amongst other genetic components. Our lab uses epigenomic approaches and molecular biology tools to investigate the epigenetic mechanisms involved in these two seemingly opposing facets of transposon biology. Our group aims to elucidate the functional roles that transposable elements play in the contexts of development, health and disease.
Lectures on Epigenetics for:
iBSc in Neuroscience
MSc in Neuroscience and Translational Medicine
ICM7142 - MSc in Regenerative Medicine
Control of TE expression
In most somatic tissues, TEs are transcriptionally repressed by a variety of mechanisms, including DNA methylation and histone modifications. We aim to better understand these mechanisms, and are particularly interested in cases where the epigenetic landscape is distinct to that seen in most somatic tissues, such as during preimplantation development.
TEs as gene regulators
Non-coding sequences within TEs harbour multiple binding sites for host transcription factors. As TEs spread throughout the genome, some of these sequences can become important regulators of host gene expression. We aim to establish causal links between TE regulatory capacity, gene expression and phenotypes.
TEs in placental evolution
The unique epigenetic landscape of the placenta presents an apparently permissive environment for TE expression, which may have led to an extensive co-option of TEs as placental genes and regulatory elements. We are dissecting the contribution of TEs to the enhancer landscape of both rodent and primate trophoblast.
Research Group members
- Jennifer Frost, Postdoctoral Research Assistant
- Samuel Amante, Postdoctoral Research Assistant
- Darren Taylor, PhD Student
Deniz O, Ahmed M, Todd CD, Rio-Machin A, Dawson MA, Branco MR# (2020) “Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia”, Nature Communications, 11:3506
Todd CD, Deniz O, Taylor D, Branco MR (2019) “Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells”, eLife, 8:e44344
Deniz O, Frost JM, Branco MR (2019) “Regulation of transposable elements by DNA modifications”, Nature Reviews Genetics, 20:417-31
Deniz O, de la Rica L, Cheng KC, Spensberger D, Branco MR (2018) “SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells”, Genome Biology, 19:6
de la Rica L, Deniz O, Cheng KC, Todd CD, Cruz C, Houseley J, Branco MR (2016) “TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells”, Genome Biology, 17:234
Darren Taylor, PhD student