It is established that chromatin domains or globules are localized in either transcriptionally repressive or permissive compartments. Here we use genome-wide and computational strategies to characterize chromatin domains during B cell development. We find that domains in the transcriptionally permissive compartment are highly enriched for transcription factor occupancy, euchromatic epigenetic marks, and SINE elements whereas those in repressive compartments are primarily associated with LINE-rich regions. The transcriptionally permissive compartment spatially segregates into distinct sub-compartments, enriched for either H3K27me3 or H3K4me2. We identify distinct classes of anchors, including CTCF and E2A, which act at different length scales and are closely associated with intra-domain and/or inter-domain interactions. We find that relocation of chromatin domains during developmental progression is closely linked with changes in lineage-specific programs of gene expression and large-scale remodeling of chromatin topology. We propose that the repositioning of chromatin domains and changes in domain topology underpin the mechanism by which a B-lineage specific program of gene expression is established.

Murre博士は、抗体遺伝子エンハンサーに結合するE2A転写因子を発見し、E2Aに存在するHelix-Loop-Helixドメインを始めて同定されました。以来、E2Aとその抑制因子であるId等による血球分化の研究で世界をリードして来られました。今回は、高次染色体構造変化によるB細胞の分化制御について、最新の知見をわかりやすく紹介していただきます。
参考文献：Cell 133: 265, 2008, Nat. Immunol. 12: 992, 2011, Nat. Immunol. 13: 1196, 2012

連絡先：生化学・分子生物学講座 分子生理化学部門　　縣　保年（内線2156）