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Histone acetylations
Histone acetylations
We investigate various histone acetylations and their role in chromatin structure and function in regulation of vertebrate genome. We particularly focus on deciphering the role of histone H4 tail acetylations (H4K16ac) and H3 tail (H3K27ac) and globular domain acetylations (H3K122ac). We are interested in deciphering the role of histone acetylation pathway in stem cells, neuronal and trophoblast lineage.
Publications:
Patel M#, Ali A#, Dabrowska A, Boulet F, Sinha AK* and Pradeepa MM* Early Prediction of Preeclampsia Based on Transposable Elements signature in cell-free RNA BioRxiv 2024.11.08.622691; doi: https://doi.org/10.1101/2024.11.08.622691 (Equal first authors)
Pal, D., Patel M., Boulet F., Sundarraj J., Grant OA., Branco MR., Basu S., Santos S., Zabet, N R., Scaffidi, P., Pradeepa, MM* H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function Nature Struct. Mol. Biol. 2023 https://rdcu.be/deluI
Olley G, Pradeepa MM, Grimes GR, Piquet S, Polo SE, FitzPatrick DR, Bickmore WA, Boumendil C. Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect. Nat Commun. 2021 May 25;12(1):3127. https://www.nature.com/articles/s41467-023-44544-w
Olley G, Ansari M, Bengani H, Grimes GR, Rhodes J, Kriegsheim AV, Blatnik A, Stewart F J, Ross A, Bickmore WA*, Pradeepa MM*, and FitzPatrick DR*. BRD4 interacts with NIPBL and is mutated in a Cornelia de Lange-like syndrome. Nature Genet. 2018. 50 (3), 329-332 https://www.nature.com/articles/s41588-018-0042-y
Marin R#, Cortez D#, Lamanna F#, Pradeepa MM#, Leushkin E, Julien P, Liechti A, Halbert J, Kerver HN, Wade J, Tschopp P and Kaessmann H (2017) Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage Genome Res, 27 (12), 1974-1987 https://genome.cshlp.org/content/27/12/1974
Pradeepa M M*, Grimes G, Kumar Y, Taylor G, Olley G, Schneider R and Bickmore W A* (2016) Histone H3 globular domain acetylation identifies a new class of enhancers. Nature Genet. 48, 681–686 https://www.nature.com/articles/ng.3550
Taylor G, Eskeland R. Balkan B H, Pradeepa M M* & Bickmore W A*. (2013) H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res. https://genome.cshlp.org/content/23/12/2053
KATS and BETs
KATS and BETs
We investigate the role of lysine acetyl transferases (KAT) and bromo- and extra-terminal domain proteins (BET), BRD4, BRD3 and BRD2 in stem cells, neuronal lineage and cancers.
Publications:
Pal, D., Patel M., Boulet F., Sundarraj J., Grant OA., Branco MR., Basu S., Santos S., Zabet, N R., Scaffidi, P., Pradeepa, MM* H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function
· Olley G, Pradeepa MM, Grimes GR, Piquet S, Polo SE, FitzPatrick DR, Bickmore WA, Boumendil C. Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect. Nat Commun. 2021 May 25;12(1):3127.
· Olley G, Ansari M, Bengani H, Grimes GR, Rhodes J, Kriegsheim AV, Blatnik A, Stewart F J, Ross A, Bickmore WA*, Pradeepa MM*, and FitzPatrick DR*. BRD4 interacts with NIPBL and is mutated in a Cornelia de Lange-like syndrome. Nature Genet. 2018. 50 (3), 329-332
Chromatin Proteins
Chromatin Proteins
We study the role of chromatin proteins associated with transcription, DNA repair. Particularly our lab has long standing interest in investigating the role of a transcriptional coactivator PSIP1 in development and diseases.
Publications:
· Sundarraj J., Patel M., Aziz H., Brooke G., Tummala H., Pradeepa MM* PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity Nature Communications 15, 361(2024) https://doi.org/10.1038/s41467-023-44544-w
· Pradeepa M M*, Grimes G, Taylor G, Sutherland H & Bickmore W A*. (2014) Psip1/p75 restrains expression of Hox genes by recruiting both trithorax and polycomb proteins. Nucleic Acid Res. DOI: 10.1093/nar/gku647.
· Pradeepa, M M., Sutherland, H. G., Ule, J., Grimes, G. R., & Bickmore, W. A. (2012). Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS genetics, 8(5), e1002717. doi:10.1371.
noncoding variants
noncoding variants
We investigate how noncoding variants at cis regulatory elements contribute to disease
We focus on cancer associated variants and variants detected in neurodevelopmental disorders
Publications:
· Patel MB, Maniati E, Atanur SS, Pal D, Rio-Machin A, Heward J, Fitzgibbon J, Pradeepa MM* & Wang J* Non-coding mutations at enhancer clusters contribute to pancreatic ductal adenocarcinoma BioRxiv 2023.06.28.546873; doi: https://doi.org/10.1101/2023.06.28.546873
De Vas MG, Boulet F. Garstang MG, Joshi SS, Khan TN, Atla G, Parry D, Moore D, Cebola I, Zhang S, Cui W, Lampe A K, Lam WW, Genomics England Consortium, Ferrer J, Pradeepa MM*, Atanur SS* Regulatory de novo mutations underlying intellectual disability Life Science Alliance 2023. DOI: 10.26508/lsa.202201843.
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