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有丝分裂Clb细胞周期蛋白是在G1/S转换期减轻酵母组蛋白基因的HIR介导的抑制作用所必需的。

The mitotic Clb cyclins are required to alleviate HIR-mediated repression of the yeast histone genes at the G1/S transition.

作者信息

Amin Amit Dipak, Dimova Dessislava K, Ferreira Monica E, Vishnoi Nidhi, Hancock Leandria C, Osley Mary Ann, Prochasson Philippe

机构信息

Department of Pathology and Laboratory Medicine, University of Kansas Medical School, Kansas City, KS, USA.

出版信息

Biochim Biophys Acta. 2012 Jan;1819(1):16-27. doi: 10.1016/j.bbagrm.2011.09.003. Epub 2011 Sep 28.

DOI:10.1016/j.bbagrm.2011.09.003
PMID:21978826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3249481/
Abstract

The histone genes are an important group of cell cycle regulated genes whose transcription is activated during the G1/S transition and repressed in early G1, late S, and G2/M. The HIR complex, comprised of Hir1, Hir2, Hir3 and Hpc2, regulates three of the four histone gene loci. While relief of repression at the G1/S boundary involves the HIR complex, as well as other cofactors, the mechanism by which this derepression occurs remains unknown. To better understand how transcriptional repression contributes to periodic expression in the cell cycle, we sought to identify the cell cycle signals required to alleviate HIR-mediated repression of the histone genes. By measuring histone gene transcription in strains with various combinations of clb mutations, we found that the mitotic Clb1/Clb2 cyclins are required to alleviate Hir-mediated repression during the G1/S transition and that Clb2 physically interacts with the HIR complex. While the HIR complex regulates histone gene transcription in combination with two other histone H3/H4 chaperones, Asf1 and Rtt106, our data demonstrate that the mitotic Clb cyclins are necessary to specifically alleviate the repressive action of the HIR complex itself in order to allow proper expression of the histone genes in late G1/early S phase.

摘要

组蛋白基因是细胞周期调控基因的一个重要类别，其转录在G1/S期转换时被激活，而在G1早期、S晚期和G2/M期被抑制。由Hir1、Hir2、Hir3和Hpc2组成的HIR复合物调控着四个组蛋白基因位点中的三个。虽然在G1/S边界处抑制的解除涉及HIR复合物以及其他辅因子，但这种去抑制发生的机制仍然未知。为了更好地理解转录抑制如何促进细胞周期中的周期性表达，我们试图确定减轻HIR介导的组蛋白基因抑制所需的细胞周期信号。通过测量具有各种clb突变组合的菌株中的组蛋白基因转录，我们发现有丝分裂期的Clb1/Clb2细胞周期蛋白是在G1/S期转换期间减轻Hir介导的抑制所必需的，并且Clb2与HIR复合物发生物理相互作用。虽然HIR复合物与另外两个组蛋白H3/H4伴侣蛋白Asf1和Rtt106共同调节组蛋白基因转录，但我们的数据表明，有丝分裂期的Clb细胞周期蛋白对于特异性减轻HIR复合物本身的抑制作用是必要的，以便在G1晚期/ S期早期使组蛋白基因能够正常表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/f44b87375881/nihms-328586-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/62ec8d4bbc9b/nihms-328586-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/1a760999c5c2/nihms-328586-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/ca371f4885f6/nihms-328586-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/491dd87de12b/nihms-328586-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/b9f666d2f3dc/nihms-328586-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/d85c603729f5/nihms-328586-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/0bca5bd9efd9/nihms-328586-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/f44b87375881/nihms-328586-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/62ec8d4bbc9b/nihms-328586-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/1a760999c5c2/nihms-328586-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/5b19a5c18071/nihms-328586-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/ca371f4885f6/nihms-328586-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/491dd87de12b/nihms-328586-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/b9f666d2f3dc/nihms-328586-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/d85c603729f5/nihms-328586-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/0bca5bd9efd9/nihms-328586-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdf1/3249481/f44b87375881/nihms-328586-f0009.jpg

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