Life Sciences Research for Lifelong Health

Kristina Tabbada

Kristina started at the Babraham Institute in 2009, with the (then) newly-established Next Generation Sequencing Facility. Prior to coming to Babraham, Kristina was a forensic genetic analyst at the DNA Analysis Laboratory (University of the Philippines). She had also studied biological anthropology and completed a masteral dissertation project involving mitochondrial DNA sequencing of human populations at the University of Cambridge. 

Latest Publications

Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination.
Bolland DJ, Koohy H, Wood AL, Matheson LS, Krueger F, Stubbington MJ, Baizan-Edge A, Chovanec P, Stubbs BA, Tabbada K, Andrews SR, Spivakov M, Corcoran AE

Variable (V), diversity (D), and joining (J) (V(D)J) recombination is the first determinant of antigen receptor diversity. Understanding how recombination is regulated requires a comprehensive, unbiased readout of V gene usage. We have developed VDJ sequencing (VDJ-seq), a DNA-based next-generation-sequencing technique that quantitatively profiles recombination products. We reveal a 200-fold range of recombination efficiency among recombining V genes in the primary mouse Igh repertoire. We used machine learning to integrate these data with local chromatin profiles to identify combinatorial patterns of epigenetic features that associate with active VH gene recombination. These features localize downstream of VH genes and are excised by recombination, revealing a class of cis-regulatory element that governs recombination, distinct from expression. We detect two mutually exclusive chromatin signatures at these elements, characterized by CTCF/RAD21 and PAX5/IRF4, which segregate with the evolutionary history of associated VH genes. Thus, local chromatin signatures downstream of VH genes provide an essential layer of regulation that determines recombination efficiency.

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Cell reports, 15, 2211-1247, 2475-87, 2016

PMID: 27264181

Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.
Schoenfelder S, Sugar R, Dimond A, Javierre BM, Armstrong H, Mifsud B, Dimitrova E, Matheson L, Tavares-Cadete F, Furlan-Magaril M, Segonds-Pichon A, Jurkowski W, Wingett SW, Tabbada K, Andrews S, Herman B, LeProust E, Osborne CS, Koseki H, Fraser P, Luscombe NM, Elderkin S

The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mouse ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox gene clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox gene network. In contrast, promoter-enhancer contacts are maintained in the absence of Polycomb repression, with accompanying widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional upregulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that the selective release of genes from this spatial network underlies cell fate specification during early embryonic development.

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Nature genetics, , 1546-1718, , 2015

PMID: 26323060

The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.
Schoenfelder S, Furlan-Magaril M, Mifsud B, Tavares-Cadete F, Sugar R, Javierre BM, Nagano T, Katsman Y, Sakthidevi M, Wingett SW, Dimitrova E, Dimond A, Edelman LB, Elderkin S, Tabbada K, Darbo E, Andrews S, Herman B, Higgs A, LeProust E, Osborne CS, Mitchell JA, Luscombe NM, Fraser P

The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression.

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Genome research, 25, 1549-5469, 582-97, 2015

PMID: 25752748

01223 496330

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Latest Publications

Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination.

Bolland DJ, Koohy H, Wood AL

Cell reports
15 2211-1247:2475-87 (2016)

PMID: 27264181

Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.

Schoenfelder S, Sugar R, Dimond A

Nature genetics
1546-1718: (2015)

PMID: 26323060

The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.

Schoenfelder S, Furlan-Magaril M, Mifsud B

Genome research
25 1549-5469:582-97 (2015)

PMID: 25752748

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