دورية أكاديمية

Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs

التفاصيل البيبلوغرافية
العنوان: Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs
المؤلفون: A. Lorzadeh, C. Hammond, F. Wang, D. J. H. F. Knapp, J. CH. Wong, J. Y. A. Zhu, Q. Cao, A. Heravi-Moussavi, A. Carles, M. Wong, Z. Sharafian, J. Steif, M. Moksa, M. Bilenky, P. M. Lavoie, C. J. Eaves, M. Hirst
المصدر: BMC Biology, Vol 20, Iss 1, Pp 1-23 (2022)
بيانات النشر: BMC, 2022.
سنة النشر: 2022
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Human hematopoietic cell differentiation, Epigenomics, H3K27me3, Hematopoietic progenitors, In vitro differentiation, Biology (General), QH301-705.5
الوصف: Abstract Background Lifelong production of the many types of mature blood cells from less differentiated progenitors is a hierarchically ordered process that spans multiple cell divisions. The nature and timing of the molecular events required to integrate the environmental signals, transcription factor activity, epigenetic modifications, and changes in gene expression involved are thus complex and still poorly understood. To address this gap, we generated comprehensive reference epigenomes of 8 phenotypically defined subsets of normal human cord blood. Results We describe a striking contraction of H3K27me3 density in differentiated myelo-erythroid cells that resembles a punctate pattern previously ascribed to pluripotent embryonic stem cells. Phenotypically distinct progenitor cell types display a nearly identical repressive H3K27me3 signature characterized by large organized chromatin K27-modification domains that are retained by mature lymphoid cells but lost in terminally differentiated monocytes and erythroblasts. We demonstrate that inhibition of polycomb group members predicted to control large organized chromatin K27-modification domains influences lymphoid and myeloid fate decisions of primary neonatal hematopoietic progenitors in vitro. We further show that a majority of active enhancers appear in early progenitors, a subset of which are DNA hypermethylated and become hypomethylated and induced during terminal differentiation. Conclusion Primitive human hematopoietic cells display a unique repressive H3K27me3 signature that is retained by mature lymphoid cells but is lost in monocytes and erythroblasts. Intervention data implicate that control of this chromatin state change is a requisite part of the process whereby normal human hematopoietic progenitor cells make lymphoid and myeloid fate decisions.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1741-7007
العلاقة: https://doaj.org/toc/1741-7007Test
DOI: 10.1186/s12915-022-01315-1
الوصول الحر: https://doaj.org/article/323a789235c74537b3d3137709c319fdTest
رقم الانضمام: edsdoj.323a789235c74537b3d3137709c319fd
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17417007
DOI:10.1186/s12915-022-01315-1