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@ARTICLE{Schnung:182554,
author = {M. Schönung$^*$ and M. Hartmann$^*$ and S. Krämer$^*$ and
S. Stäble$^*$ and M. Hakobyan$^*$ and E. Kleinert$^*$ and
T. Aurich$^*$ and D. Cobanoglu$^*$ and F. H. Heidel and S.
Fröhling$^*$ and M. D. Milsom$^*$ and M. Schlesner and P.
Lutsik$^*$ and D. Lipka$^*$},
title = {{D}ynamic {DNA} methylation reveals novel cis-regulatory
elements in mouse hematopoiesis.},
journal = {Experimental hematology},
volume = {117},
issn = {0301-472X},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2022-02735},
pages = {24-42.e7},
year = {2023},
note = {#EA:B340#LA:B340# / 2023 Jan;117:24-42.e7},
abstract = {Differentiation of hematopoietic stem and progenitor cells
(HSPCs) to terminally differentiated immune cells is
accompanied by large-scale remodeling of the DNA methylation
landscape. While significant insights into the molecular
mechanisms of hematopoietic tissue regeneration were derived
from mouse models, profiling of DNA methylation has been
hampered by high cost or low resolution using the methods
available. This problem has been overcome by the recent
development of the Infinium Mouse Methylation BeadChip
(MMBC) array, facilitating methylation profiling of the
mouse genome at single CpG resolution at affordable cost. We
extended the RnBeads package to provide a computational
framework for the analysis of MMBC data. This framework was
applied to a newly generated reference map of mouse
hematopoiesis encompassing nine different cell types. The
analysis of dynamically regulated CpG sites showed
progressive and unidirectional DNA methylation changes from
HSPCs to differentiated hematopoietic cells and allowed the
identification of lineage- and cell type-specific DNA
methylation programs. Comparison to previously published
catalogues of cis-regulatory elements (CREs) revealed 12,856
novel putative CREs which were dynamically regulated by DNA
methylation (mdCREs). These mdCREs were predominantly
associated with patterns of cell type-specific DNA
hypomethylation and could be identified as epigenetic
control regions regulating the expression of key
hematopoietic genes during differentiation. In summary, we
established an analysis pipeline for MMBC datasets and
provide a DNA methylation atlas of mouse hematopoiesis. This
resource allowed us to identify novel putative CREs involved
in hematopoiesis and will serve as a platform to study
epigenetic regulation of normal and malignant
hematopoiesis.},
keywords = {285k methylation array (Other) / DNA methylation (Other) /
cis regulatory elements (Other) / epigenetics (Other) /
hematopoiesis (Other) / hematopoietic stem cells (Other) /
mouse methylation bead chip (Other)},
cin = {B340 / A012 / B370},
ddc = {610},
cid = {I:(DE-He78)B340-20160331 / I:(DE-He78)A012-20160331 /
I:(DE-He78)B370-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36368558},
doi = {10.1016/j.exphem.2022.11.001},
url = {https://inrepo02.dkfz.de/record/182554},
}