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PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
by
Schmidt, Christin
, Northcott, Paul A.
, Phillips, Joanna J.
, Weiss, William A.
, Carlson, Annika
, Cohen, Sarah
, Westelman, Samantha
, Gudenas, Brian L.
, Husain, Sarah
, Wang, Linyu
, Schwer, Bjoern
in
631/208
/ 631/67
/ Animals
/ Cell Line, Tumor
/ Cerebellar Neoplasms - genetics
/ Cerebellar Neoplasms - metabolism
/ Cerebellar Neoplasms - pathology
/ Chromatin
/ Chromatin - genetics
/ Chromatin - metabolism
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene mapping
/ Hindbrain
/ Histone H3
/ Histone-Lysine N-Methyltransferase - genetics
/ Histone-Lysine N-Methyltransferase - metabolism
/ Histones
/ Histones - metabolism
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Medulloblastoma
/ Medulloblastoma - genetics
/ Medulloblastoma - metabolism
/ Medulloblastoma - pathology
/ Methylation
/ multidisciplinary
/ Neuroepithelial Cells - metabolism
/ Science
/ Science (multidisciplinary)
/ Stem cells
/ Transcription factors
2024
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PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
by
Schmidt, Christin
, Northcott, Paul A.
, Phillips, Joanna J.
, Weiss, William A.
, Carlson, Annika
, Cohen, Sarah
, Westelman, Samantha
, Gudenas, Brian L.
, Husain, Sarah
, Wang, Linyu
, Schwer, Bjoern
in
631/208
/ 631/67
/ Animals
/ Cell Line, Tumor
/ Cerebellar Neoplasms - genetics
/ Cerebellar Neoplasms - metabolism
/ Cerebellar Neoplasms - pathology
/ Chromatin
/ Chromatin - genetics
/ Chromatin - metabolism
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene mapping
/ Hindbrain
/ Histone H3
/ Histone-Lysine N-Methyltransferase - genetics
/ Histone-Lysine N-Methyltransferase - metabolism
/ Histones
/ Histones - metabolism
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Medulloblastoma
/ Medulloblastoma - genetics
/ Medulloblastoma - metabolism
/ Medulloblastoma - pathology
/ Methylation
/ multidisciplinary
/ Neuroepithelial Cells - metabolism
/ Science
/ Science (multidisciplinary)
/ Stem cells
/ Transcription factors
2024
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PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
by
Schmidt, Christin
, Northcott, Paul A.
, Phillips, Joanna J.
, Weiss, William A.
, Carlson, Annika
, Cohen, Sarah
, Westelman, Samantha
, Gudenas, Brian L.
, Husain, Sarah
, Wang, Linyu
, Schwer, Bjoern
in
631/208
/ 631/67
/ Animals
/ Cell Line, Tumor
/ Cerebellar Neoplasms - genetics
/ Cerebellar Neoplasms - metabolism
/ Cerebellar Neoplasms - pathology
/ Chromatin
/ Chromatin - genetics
/ Chromatin - metabolism
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene mapping
/ Hindbrain
/ Histone H3
/ Histone-Lysine N-Methyltransferase - genetics
/ Histone-Lysine N-Methyltransferase - metabolism
/ Histones
/ Histones - metabolism
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Medulloblastoma
/ Medulloblastoma - genetics
/ Medulloblastoma - metabolism
/ Medulloblastoma - pathology
/ Methylation
/ multidisciplinary
/ Neuroepithelial Cells - metabolism
/ Science
/ Science (multidisciplinary)
/ Stem cells
/ Transcription factors
2024
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PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
Journal Article
PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
2024
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Overview
SNCAIP
duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the
PRDF1 and RIZ1 homology domain-containing
(PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/67
/ Animals
/ Cerebellar Neoplasms - genetics
/ Cerebellar Neoplasms - metabolism
/ Cerebellar Neoplasms - pathology
/ Gene Expression Regulation, Neoplastic
/ Histone-Lysine N-Methyltransferase - genetics
/ Histone-Lysine N-Methyltransferase - metabolism
/ Histones
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Medulloblastoma - metabolism
/ Neuroepithelial Cells - metabolism
/ Science
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