Carmen Salvador-Palomeque started her studies in Biology at the University of Granada in Spain. In 2010 she specialized in Genetics at the Complutense University of Madrid. She obtained a Master Degree in Biochemistry, Molecular Biology and Biomedicine in the School of Chemistry in 2012 at the Complutense University of Madrid. She was interested in Cancer Research and she did her Master’s thesis in the School of Medicine at the Department of Anatomy and Human Embryology on “Characterisation of the transcriptional activity of MyoR and Capsulin”. In the same lab she defended her Tesina in 2012 (equivalent to a PhD mid candidature) on “Cloning and characterizing Polycomb genes during chick development”. From 2013 to 2014 she joined Dr. Jose Luis Garcia-Perez’s lab in GENYO (Pfizer-University of Granada and Andalusian Government Centre for Genomics and Oncology) and started to study LINE-1 activity in Hepatocellular Carcinoma (HCC) and also the interaction of LINE-1 and Tex19.1 in the mammalian germline. In 2014,she obtained an International Scholarship at the University of Queensland (UQI) and joined Prof. Geoffrey J Faulkner’s lab. Carmen’s PhD is focused on the study of LINE-1 activity in neurogenesis and also on the study of LINE-1 activity in Rett syndrome and Ataxia Telangiectasia.
Salvador-Palomeque, Carmen; Sanchez-Luque, Francisco J; Fortuna, Patrick R J; Ewing, Adam D; Wolvetang, Ernst J; Richardson, Sandra R; Faulkner, Geoffrey J
In: Mol Cell Biol, 39 (7), 2019, ISSN: 0270-7306.
(| | | )
The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells., The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neuronal lineage and cause somatic mosaicism. Although DNA methylation mediates L1 promoter repression, the temporal pattern of methylation applied to individual RC-L1s during neurogenesis is unclear. Here, we identified a de novo L1 insertion in a human induced pluripotent stem cell (hiPSC) line via retrotransposon capture sequencing (RC-seq). The L1 insertion was full-length and carried 5ʹ and 3ʹ transductions. The corresponding donor RC-L1 was part of a large and recently active L1 transduction family and was highly mobile in a cultured-cell L1 retrotransposition reporter assay. Notably, we observed distinct and dynamic DNA methylation profiles for the de novo L1 and members of its extended transduction family during neuronal differentiation. These experiments reveal how a de novo L1 insertion in a pluripotent stem cell is rapidly recognized and repressed, albeit incompletely, by the host genome during neurodifferentiation, while retaining potential for further retrotransposition.
Sanchez-Luque, Francisco J; Kempen, Marie-Jeanne H C; Gerdes, Patricia; Vargas-Landin, Dulce B; Richardson, Sandra R; Troskie, Robin-Lee; Jesuadian, Samuel J; Cheetham, Seth W; Carreira, Patricia E; Salvador-Palomeque, Carmen; García-Cañadas, Marta; Muñoz-Lopez, Martin; Sanchez, Laura; Lundberg, Mischa; Macia, Angela; Heras, Sara R; Brennan, Paul M; Lister, Ryan; Garcia-Perez, Jose L; Ewing, Adam D; Faulkner, Geoffrey J
LINE-1 Evasion of Epigenetic Repression in Humans (Journal Article)
In: Molecular Cell, 0 (0), 2019, ISSN: 1097-2765.
(| | | )
textlessh2textgreaterSummarytextless/h2textgreatertextlessptextgreaterEpigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3ʹ transduction. The source (donor) L1 for this insertion was slightly 5ʹ truncated, lacked the YY1 binding site, and was highly mobile when tested textitin vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.textless/ptextgreater
Upton, Kyle R; Gerhardt, Daniel J; Jesuadian, Samuel J; Richardson, Sandra R; Sánchez-Luque, Francisco J; Bodea, Gabriela O; Ewing, Adam D; Salvador-Palomeque, Carmen; van der Knaap, Marjo S; Brennan, Paul M; Vanderver, Adeline; Faulkner, Geoffrey J
Ubiquitous L1 mosaicism in hippocampal neurons (Journal Article)
In: Cell, 161 (2), pp. 228–239, 2015.
(| | )
Somatic LINE-1 (L1) retrotransposition during neurogenesis is
a potential source of genotypic variation among neurons. As a
neurogenic niche, the hippocampus supports pronounced L1
activity. However, the basal parameters and biological impact
of L1-driven mosaicism remain unclear. Here, we performed
single-cell retrotransposon capture sequencing (RC-seq) on
individual human hippocampal neurons and glia, as well as
cortical neurons. An estimated 13.7 somatic L1 insertions
occurred per hippocampal neuron and carried the sequence
hallmarks of target-primed reverse transcription. Notably,
hippocampal neuron L1 insertions were specifically enriched in
transcribed neuronal stem cell enhancers and hippocampus
genes, increasing their probability of functional relevance.
In addition, bias against intronic L1 insertions sense
oriented relative to their host gene was observed, perhaps
indicating moderate selection against this configuration in
vivo. These experiments demonstrate pervasive L1 mosaicism at
genomic loci expressed in hippocampal neurons.
Richardson, Sandra R; Salvador-Palomeque, Carmen; Faulkner, Geoffrey J
In: Bioessays, 36 (5), pp. 475–481, 2014.
(| | )
Gene retrocopies are generated by reverse transcription and
genomic integration of mRNA. As such, retrocopies present an
important exception to the central dogma of molecular biology,
and have substantially impacted the functional landscape of
the metazoan genome. While an estimated 8,000-17,000
retrocopies exist in the human genome reference sequence, the
extent of variation between individuals in terms of retrocopy
content has remained largely unexplored. Three recent studies
by Abyzov et al., Ewing et al. and Schrider et al. have
exploited 1,000 Genomes Project Consortium data, as well as
other sources of whole-genome sequencing data, to uncover
novel gene retrocopies. Here, we compare the methods and
results of these three studies, highlight the impact of
retrocopies in human diversity and genome evolution, and
speculate on the potential for somatic gene retrocopies to
impact cancer etiology and genetic diversity among individual
neurons in the mammalian brain.
- Click to share on Twitter (Opens in new window)
- Click to share on Facebook (Opens in new window)
- Click to share on Skype (Opens in new window)
- Click to share on Tumblr (Opens in new window)
- Click to share on Pinterest (Opens in new window)
- Click to share on Pocket (Opens in new window)
- Click to print (Opens in new window)