DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription

Feng，Weimin1; Chen，Shiyun1; Wang，Jiuling1; Wang，Xingshun1; Chen，Huaiyong2,3; Ning，Wen4; Zhang，Yandong1,5

2020-06-15

10.1128/MCB.00460-19

MOLECULAR AND CELLULAR BIOLOGY   影响因子和分区

0270-7306

1098-5549

RNA helicase DHX33 was found to regulate the transcription of multiple genes involved in cancer development. But the underlying molecular mechanism remains unclear. Here, we found DHX33 associated extensively with gene promoters at CG-rich region. Its deficiency reduced the loading of active RNA polymerase II at gene promoters. Furthermore, we observed a functional interaction between DHX33, AP-2β, and DNA demethylation protein Gadd45a (growth arrest and DNA damage inductile protein 45a) at specific gene promoters. DHX33 is required to recruit GADD45a, thereby causing local DNA demethylation through further recruiting ten-eleven-translocation (Tet) methylcytosine dioxygenase enzyme, as manifested by reduced 5-hydroxymethyl cytosine levels for a subset of genes after DHX33 deficiency. This process might involve R-loop formation in GC skew as a guidance signal at promoter sites. Our report provides for the first time, to our knowledge, original evidence that DHX33 alters epigenetic marks and regulates specific gene transcription through interaction with Gadd45a.

Aurora kinase CpG islands demethylation DHX33 Gadd45a RNA helicase

SCI

英语

第一

Science and Technology Innovation Committee of Shenzhen Municipality[JCYJ20170307110713487][CKCY2017072116462727] ; Guangdong Provincial Science and Technology Department[2017A020211024]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000579012400005

AMER SOC MICROBIOLOGY

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85086524525

Scopus

1.Department of Biology,Southern University of Science and Technology,Shenzhen,China
2.Department of Basic Medicine,Haihe Clinic College of Tianjin Medical University,China
3.Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine,Tianjin Institute of Respiratory Diseases,Tianjin Haihe Hospital,China
4.School of Life Sciences,Nankai University,China
5.Shenzhen KeYe Life Technologies,Co.,Ltd.,Shenzhen,China

Feng，Weimin,Chen，Shiyun,Wang，Jiuling,et al. DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription[J]. MOLECULAR AND CELLULAR BIOLOGY,2020,40(13).

Feng，Weimin.,Chen，Shiyun.,Wang，Jiuling.,Wang，Xingshun.,Chen，Huaiyong.,...&Zhang，Yandong.(2020).DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription.MOLECULAR AND CELLULAR BIOLOGY,40(13).

Feng，Weimin,et al."DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription".MOLECULAR AND CELLULAR BIOLOGY 40.13(2020).