RRC ID 69651
著者 Ishikura S, Nakabayashi K, Nagai M, Tsunoda T, Shirasawa S.
タイトル ZFAT binds to centromeres to control noncoding RNA transcription through the KAT2B-H4K8ac-BRD4 axis.
ジャーナル Nucleic Acids Res
Abstract Centromeres are genomic regions essential for faithful chromosome segregation. Transcription of noncoding RNA (ncRNA) at centromeres is important for their formation and functions. Here, we report the molecular mechanism by which the transcriptional regulator ZFAT controls the centromeric ncRNA transcription in human and mouse cells. Chromatin immunoprecipitation with high-throughput sequencing analysis shows that ZFAT binds to centromere regions at every chromosome. We find a specific 8-bp DNA sequence for the ZFAT-binding motif that is highly conserved and widely distributed at whole centromere regions of every chromosome. Overexpression of ZFAT increases the centromeric ncRNA levels at specific chromosomes, whereas its silencing reduces them, indicating crucial roles of ZFAT in centromeric transcription. Overexpression of ZFAT increases the centromeric levels of both the histone acetyltransferase KAT2B and the acetylation at the lysine 8 in histone H4 (H4K8ac). siRNA-mediated knockdown of KAT2B inhibits the overexpressed ZFAT-induced increase in centromeric H4K8ac levels, suggesting that ZFAT recruits KAT2B to centromeres to induce H4K8ac. Furthermore, overexpressed ZFAT recruits the bromodomain-containing protein BRD4 to centromeres through KAT2B-mediated H4K8ac, leading to RNA polymerase II-dependent ncRNA transcription. Thus, ZFAT binds to centromeres to control ncRNA transcription through the KAT2B-H4K8ac-BRD4 axis.
巻・号 48(19)
ページ 10848-10866
公開日 2020-11-4
DOI 10.1093/nar/gkaa815
PII 5913297
PMID 32997115
PMC PMC7641738
MeSH Animals Cell Cycle Proteins / metabolism Cell Line Centromere / metabolism* Chromosome Segregation Gene Expression Regulation Histones / metabolism Humans Mice Protein Binding RNA, Untranslated / metabolism* Transcription Factors / metabolism* Transcription, Genetic p300-CBP Transcription Factors / metabolism
IF 11.502
リソース情報
遺伝子材料 pEGFPC3_EGFP-hZFAT-HA (ZF-C delta-3) (RDB19340) pEBMulti_HA-hZFAT (RDB19324) pEGFPN1_HA-hZFAT-EGFP (RDB19325) pEGFPC3_EGFP-hZFAT (RDB19326) pmCherryC3_mCherry-hZFAT (RDB19327) pcDNA3_hZFAT-HA (RDB19328) pCMV_mZfat-HA (RDB19329) pcDNA3_hZFAT-HA (ZF-N delta-1) (RDB19330) pcDNA3_hZFAT-HA (ZF-N delta-2) (RDB19331) pcDNA3_hZFAT-HA (ZF-N delta-3) (RDB19332) pcDNA3_hZFAT-HA (ZF-N delta-4) (RDB19333) pcDNA3_hZFAT-HA (ZF-C delta-1) (RDB19334) pcDNA3_hZFAT-HA (ZF-C delta-2) (RDB19335) pcDNA3_hZFAT-HA (ZF-C delta-3) (RDB19336) pcDNA3_hZFAT-HA (delta71-83) (RDB19337) pcDNA3_hZFAT-HA (GRP/AAA) (RDB19338) pEGFPC3_EGFP-hZFAT-HA (ZF-C delta-2) (RDB19339) pEGFPC3_EGFP-hBRD4 (RDB19341) pEGFPC3_nlsEGFP-BD1 (RDB19342) pEGFPC3_nlsEGFP-BD2 (RDB19343) pEGFPC3_EGFP-BD1+2 (RDB19344) pEGFPC3_EGFP-deltaBD1 (RDB19345) pEGFPC3_EGFP-deltaBD2 (RDB19346) pEGFPC3_EGFP-deltaBD1+2 (RDB19347) pcDNA3_FLAG-mKAT2B (RDB19348) pMSCV_FLAG-mKAT2B (RDB19349) pGL4.14-E1bTATA (RDB19350) pGL4_alpha-satellite-ZFAT box-1 (RDB19351) pGL4_alpha-satellite-ZFAT box-2 (RDB19352) pGL4_alpha-satellite-ZFAT box-3 (RDB19353) pGL4_alpha-satellite-ZFAT box-4 (RDB19354) pGL4_alpha-satellite-mutZFAT box (RDB19355) pGL4_Minor satellite (RDB19356)