生物
基因组
编码
遗传学
CTCF公司
基因
基因间区
转录因子
抄写(语言学)
发起人
计算生物学
基因组组织
进化生物学
增强子
基因表达
语言学
哲学
作者
Giriram Mohana,Julien Dorier,Xiao Li,Marion Mouginot,Rebecca C. Smith,Héléna Malek,Marion Leleu,Daniel A. Rodriguez,Jenisha Khadka,Philippe La Rosa,Pascal Cousin,Christian Iseli,Simon Restrepo,Nicolas Guex,Brian D. McCabe,Aleksander Jankowski,Michael Levine,Maria Cristina Gambetta
出处
期刊:Cell
[Elsevier]
日期:2023-08-01
卷期号:186 (18): 3826-3844.e26
被引量:17
标识
DOI:10.1016/j.cell.2023.07.008
摘要
Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired. The associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. These long-range associations occur in a large fraction of neurons but support transcription in only a subset of neurons. Meta-domains are formed by diverse transcription factors that are able to pair over long and flexible distances. We present evidence that two such factors, GAF and CTCF, play direct roles in this process. The relative simplicity of higher-order meta-domain interactions in Drosophila, compared with those previously described in mammals, allowed the demonstration that genomes can fold into highly specialized cell-type-specific scaffolds that enable megabase-scale regulatory associations.
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