Alterations of Specific Chromatin Conformation Affect ATRA-Induced Leukemia Cell Differentiation

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dc.contributor.ISNI0000 0001 1707 1372 (Zhang, MQ)
dc.contributor.authorLi, Yanjian
dc.contributor.authorHe, Yi
dc.contributor.authorLiang, Zhengyu
dc.contributor.authorWang, Yang
dc.contributor.authorChen, Fengling
dc.contributor.authorDjekidel, Mohamed Nadhir
dc.contributor.authorLi, Guipeng
dc.contributor.authorZhang, Xu
dc.contributor.authorXiang, Shuqin
dc.contributor.authorWang, Zejun
dc.contributor.authorGao, Juntao
dc.contributor.authorZhang, Michael Q.
dc.contributor.authorChen, Yang
dc.contributor.utdAuthorZhang, Michael Q.
dc.date.accessioned2019-05-03T20:16:41Z
dc.date.available2019-05-03T20:16:41Z
dc.date.created2018-02-08
dc.descriptionIncludes supplementary material
dc.description.abstractChromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model. The results showed that the boundaries of topological associated domains (TADs) were stable during differentiation; however, the chromatin conformations within several specific TADs were obviously changed. By combining H3K4me3, H3K27ac, and Hi-C signals, we annotated the differential gene- regulatory chromatin interactions upon ATRA induction. The gains and losses of the gene-regulatory chromatin interactions are significantly correlated with gene expression and chromatin accessibility. Finally, we found that the loss of GATA2 expression and DNA binding are crucial for the differentiation process, and changes in the chromatin structure around the GATA2 regulate its expression upon ATRA induction. This study provided both statistical insights and experimental details regarding the relationship between chromatin conformation changes and transcription regulation during leukemia cell differentiation, and the results suggested that the chromatin conformation is a new type of potential drug target for cancer therapy.
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.departmentCenter for Systems Biology
dc.description.sponsorshipNational Basic Research Program of China [2017YFA0505503], National Nature Science Foundation of China [91729301, 31671384, 31301044 and 81630103], Beijing Natural Science Foundation [7151009],
dc.identifier.bibliographicCitationLi, Yanjian, Yi He, Zhengyu Liang, Yang Wang, et al. 2018. "Alterations of specific chromatin conformation affect ATRA-induced leukemia cell differentiation." Cell Death & Disease 9(2): 200-1 to 15, doi:10.1038/s41419-017-0173-6
dc.identifier.issn2041-4889
dc.identifier.issue2
dc.identifier.urihttps://hdl.handle.net/10735.1/6459
dc.identifier.volume9
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.urihttp://dx.doi.org/10.1038/s41419-017-0173-6
dc.rightsCC BY 4.0 (Attribution)
dc.rights©2018 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.journalCell Death & Disease
dc.subjectTretinoin
dc.subjectLeukemia, Myeloid
dc.subjectGenome, Human
dc.subjectTranscription, Genetic
dc.subjectGene Expression Regulation
dc.subjectDown-regulation
dc.subjectBreast Neoplasms
dc.subjectHl-60 Cells
dc.subjectCell Biology
dc.titleAlterations of Specific Chromatin Conformation Affect ATRA-Induced Leukemia Cell Differentiation
dc.type.genrearticle

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Zhang, Michael Q.