The Myc-associated zinc finger protein (MAZ) works together with CTCF to control cohesin positioning and genome organization.

The Myc-associated zinc finger protein (MAZ) works together with CTCF to control cohesin positioning and genome organization.
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DOI:
10.1073/pnas.2023127118
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发表时间:
2021-02-16
影响因子:
11.1
通讯作者:
Felsenfeld G
Felsenfeld G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xiao T;Li X;Felsenfeld G

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The protein CTCF plays a major role in large-scale organization of the genome. Binding sites for the protein MAZ are found adjacent to many CTCF sites. We show that, at such double sites, MAZ stabilizes CTCF binding. MAZ, like CTCF, acts independently as an “insulator” element to block the effects of a distal enhancer on a promoter, and, like CTCF, it can block the advance of a transcribing RNA polymerase II, leading to alternative RNA splicing patterns. Depletion of MAZ causes loss of short-range interactions within the nucleus and disruption of some longer-range interactions. Thus, MAZ plays a complementary role to CTCF in the nucleus, enhancing the organizational properties of CTCF and displaying many functions related to genome organization. The Myc-associated zinc finger protein (MAZ) is often found at genomic binding sites adjacent to CTCF, a protein which affects large-scale genome organization through its interaction with cohesin. We show here that, like CTCF, MAZ physically interacts with a cohesin subunit and can arrest cohesin sliding independently of CTCF. It also shares with CTCF the ability to independently pause the elongating form of RNA polymerase II, and consequently affects RNA alternative splicing. CTCF/MAZ double sites are more effective at sequestering cohesin than sites occupied only by CTCF. Furthermore, depletion of CTCF results in preferential loss of CTCF from sites not occupied by MAZ. In an assay for insulation activity like that used for CTCF, binding of MAZ to sites between an enhancer and promoter results in down-regulation of reporter gene expression, supporting a role for MAZ as an insulator protein. Hi-C analysis of the effect of MAZ depletion on genome organization shows that local interactions within topologically associated domains (TADs) are disrupted, as well as contacts that establish the boundaries of individual TADs. We conclude that MAZ augments the action of CTCF in organizing the genome, but also shares properties with CTCF that allow it to act independently.
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