Epigenetic-genetic chromatin footprinting identifies novel and subject-specific genes active in prefrontal cortex neurons

被引：11

作者：

Gusev, Fedor E. ^{[1
,3
,4
]}

Reshetov, Denis A. ^{[3
,4
]}

Mitchell, Amanda C. ^{[6
]}

Andreeva, Tatiana, V ^{[3
,4
]}

Dincer, Aslihan ^{[6
,7
]}

Grigorenko, Anastasia P. ^{[1
,3
,4
]}

Fedonin, Gennady ^{[3
]}

Halene, Tobias ^{[6
,7
]}

Aliseychik, Maria ^{[3
,8
]}

Goltsov, Andrey Y. ^{[3
]}

Solovyev, Victor ^{[5
]}

Brizgalov, Leonid ^{[4
]}

Filippova, Elena ^{[1
]}

Weng, Zhiping ^{[2
]}

Akbarian, Schahram ^{[1
,6
,7
]}

Rogaev, Evgeny, I ^{[1
,3
,8
,9
]}

机构：

[1] Univ Massachusetts, Med Sch, Dept Psychiat, Shrewsbury, MA 01545 USA

[2] Univ Massachusetts, Med Sch, Program Bioinformat & Integrat Biol, Shrewsbury, MA 01545 USA

[3] Russian Acad Sci, Dept Human Genet & Genom, Lab Evolutionary Genom, Vavilov Inst Gen Genet, Moscow, Russia

[4] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Ctr Brain Neurobiol & Neurogenet, Novosibirsk, Russia

[5] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Dept Cell Biol, Novosibirsk, Russia

[6] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY 10029 USA

[8] Lomonosov Moscow State Univ, Ctr Genet & Genet Technol, Fac Biol, Moscow, Russia

[9] Lomonosov Moscow State Univ, Fac Bioengn & Bioinformat, Moscow, Russia

来源：

FASEB JOURNAL | 2019年 / 33卷 / 07期

基金：

俄罗斯基础研究基金会; 美国国家卫生研究院;

关键词：

ChIP-seq; H3K4me3; brain; histone; TRANSCRIPTION FACTOR; EXPRESSION ANALYSIS; READ ALIGNMENT; HUMAN BRAIN; EVOLUTION; SEQUENCE; BINDING; ARCHITECTURE; ASSOCIATION; DATABASE;

D O I：

10.1096/fj.201802646R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human prefrontal cortex (PFC) is associated with broad individual variabilities in functions linked to personality, social behaviors, and cognitive functions. The phenotype variabilities associated with brain functions can be caused by genetic or epigenetic factors. The interactions between these factors in human subjects is, as of yet, poorly understood. The heterogeneity of cerebral tissue, consisting of neuronal and nonneuronal cells, complicates the comparative analysis of gene activities in brain specimens. To approach the underlying neurogenomic determinants, we performed a deep analysis of open chromatin-associated histone methylation in PFC neurons sorted from multiple human individuals in conjunction with whole-genome and transcriptome sequencing. Integrative analyses produced novel unannotated neuronal genes and revealed individual-specific chromatin blueprints of neurons that, in part, relate to genetic background. Surprisingly, we observed gender-dependent epigenetic signals, implying that gender may contribute to the chromatin variabilities in neurons. Finally, we found epigenetic, allele-specific activation of the testis-specific gene nucleoporin 210 like (NUP210L) in brain in some individuals, which we link to a genetic variant occurring in <3% of the human population. Recently, the NUP210L locus has been associated with intelligence and mathematics ability. Our findings highlight the significance of epigenetic-genetic footprinting for exploring neurologic function in a subject-specific manner.-Gusev, F. E., Reshetov, D. A., Mitchell, A. C., Andreeva, T. V., Dincer, A., Grigorenko, A. P., Fedonin, G., Halene, T., Aliseychik, M., Goltsov, A. Y., Solovyev, V., Brizgalov, L., Filippova, E., Weng, Z., Akbarian, S., Rogaev, E. I. Epigenetic-genetic chromatin footprinting identifies novel and subject-specific genes active in prefrontal cortex neurons.

引用

页码：8161 / 8173

页数：13