ZFAT binds to centromeres to control noncoding RNA transcription through the KAT2B-H4K8ac-BRD4 axis.
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
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 11 2020
04 11 2020
Historique:
accepted:
17
09
2020
revised:
09
09
2020
received:
02
06
2020
pubmed:
1
10
2020
medline:
20
11
2020
entrez:
30
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32997115
pii: 5913297
doi: 10.1093/nar/gkaa815
pmc: PMC7641738
doi:
Substances chimiques
BRD4 protein, human
0
Cell Cycle Proteins
0
Histones
0
RNA, Untranslated
0
Transcription Factors
0
ZFAT protein, human
0
ZFAT protein, mouse
0
KAT2B protein, human
EC 2.3.1.48
p300-CBP Transcription Factors
EC 2.3.1.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10848-10866Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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