Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
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DOI：
10.1093/nar/gkt035
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发表时间：
2013-03-01
影响因子：
14.9
通讯作者：
Renkawitz R
中科院分区：
文献类型：
--
作者：
Günther K;Rust M;Leers J;Boettger T;Scharfe M;Jarek M;Bartkuhn M;Renkawitz R
核小体重构和去乙酰化（NuRD）复合物的异质集合可分为含有MBD2或含有mbd3的复合物MBD2- NuRD和MBD3-NuRD。已知MBD2在体外与甲基化的CpG序列结合，而MBD3则相反。虽然已经描述了功能差异，但在全基因组结合和功能方面缺乏MBD2和MBD3的直接比较。在这里，我们表明MBD2-NuRD，与MBD3-NuRD相反，将具有常染色质修饰的开放染色质转化为具有抑制性组蛋白标记的紧密紧密的染色质。在全基因组范围内，发现MBD2在甲基化的CpG序列上富集，而MBD3结合的CpG则没有甲基化。与mbd3结合基因相比，mbd2结合基因的表达量普遍较低。当消耗细胞中的MBD2时，MBD2结合基因的活性增加，而MBD2 + mbd3结合基因的活性降低。最引人注目的是，MBD3在活性启动子上富集，而MBD2在甲基化启动子上结合，并在活性基因的外显子序列上富集。
The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2–NuRD and MBD3–NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here, we show that MBD2–NuRD, in contrast to MBD3–NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks. Genome-wide, a strong enrichment for MBD2 at methylated CpG sequences is found, whereas CpGs bound by MBD3 are devoid of methylation. MBD2-bound genes are generally lower expressed as compared with MBD3-bound genes. When depleting cells for MBD2, the MBD2-bound genes increase their activity, whereas MBD2 plus MBD3-bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes.
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影响因子：
3
作者：
Feng X;Grossman R;Stein L
通讯作者：
Stein L
影响因子：
--
作者：
Hayakawa T;Nakayama J
通讯作者：
Nakayama J
影响因子：
10.5
作者：
Hendrich, B;Guy, J;Bird, A
通讯作者：
Bird, A
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
DOI：
10.1073/pnas.1015341108
发表时间：
2011-05-03
影响因子：
11.1
作者：
Gnanapragasam, Merlin Nithya;Scarsdale, J. Neel;Williams, David C., Jr.
通讯作者：
Williams, David C., Jr.