Runx1在血细胞发育中的结构与功能

Runx1 Structure and Function in Blood Cell Development.

作者信息

Bonifer Constanze, Levantini Elena, Kouskoff Valerie, Lacaud Georges

机构信息

Institute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Beth Israel Diaconess Medical Center, Harvard Medical School, Boston, MA, USA.

出版信息

Adv Exp Med Biol. 2017;962:65-81. doi: 10.1007/978-981-10-3233-2_5.

DOI:10.1007/978-981-10-3233-2_5

PMID:28299651

Abstract

RUNX transcription factors belong to a highly conserved class of transcriptional regulators which play various roles in the development of the majority of metazoans. In this review we focus on the founding member of the family, RUNX1, and its role in the transcriptional control of blood cell development in mammals. We summarize data showing that RUNX1 functions both as activator and repressor within a chromatin environment, a feature that requires its interaction with multiple other transcription factors and co-factors. Furthermore, we outline how RUNX1 works together with other factors to reshape the epigenetic landscape and the three-dimensional structure of gene loci within the nucleus. Finally, we review how aberrant forms of RUNX1 deregulate blood cell development and cause hematopoietic malignancies.

摘要

RUNX转录因子属于一类高度保守的转录调节因子，在大多数后生动物的发育过程中发挥着多种作用。在本综述中，我们重点关注该家族的创始成员RUNX1及其在哺乳动物血细胞发育转录调控中的作用。我们总结了相关数据，这些数据表明RUNX1在染色质环境中既作为激活剂又作为抑制剂发挥作用，这一特性要求它与多种其他转录因子和辅助因子相互作用。此外，我们概述了RUNX1如何与其他因子协同作用，以重塑细胞核内基因位点的表观遗传格局和三维结构。最后，我们回顾了RUNX1的异常形式如何失调血细胞发育并导致造血系统恶性肿瘤。