TY - JOUR

T1 - Genome-wide analysis of gene regulation mechanisms during Drosophila spermatogenesis

AU - Laktionov, Petr P.

AU - Maksimov, Daniil A.

AU - Romanov, Stanislav E.

AU - Antoshina, Polina A.

AU - Posukh, Olga V.

AU - White-Cooper, Helen

AU - Koryakov, Dmitry E.

AU - Belyakin, Stepan N.

N1 - Publisher Copyright: © 2018 The Author(s).

PY - 2018/4/2

Y1 - 2018/4/2

N2 - Background: During Drosophila spermatogenesis, testis-specific meiotic arrest complex (tMAC) and testis-specific TBP-associated factors (tTAF) contribute to activation of hundreds of genes required for meiosis and spermiogenesis. Intriguingly, tMAC is paralogous to the broadly expressed complex Myb-MuvB (MMB)/dREAM and Mip40 protein is shared by both complexes. tMAC acts as a gene activator in spermatocytes, while MMB/dREAM was shown to repress gene activity in many cell types. Results: Our study addresses the intricate interplay between tMAC, tTAF, and MMB/dREAM during spermatogenesis. We used cell type-specific DamID to build the DNA-binding profiles of Cookie monster (tMAC), Cannonball (tTAF), and Mip40 (MMB/dREAM and tMAC) proteins in male germline cells. Incorporating the whole transcriptome analysis, we characterized the regulatory effects of these proteins and identified their gene targets. This analysis revealed that tTAFs complex is involved in activation of achi, vis, and topi meiosis arrest genes, implying that tTAFs may indirectly contribute to the regulation of Achi, Vis, and Topi targets. To understand the relationship between tMAC and MMB/dREAM, we performed Mip40 DamID in tTAF- and tMAC-deficient mutants demonstrating meiosis arrest phenotype. DamID profiles of Mip40 were highly dynamic across the stages of spermatogenesis and demonstrated a strong dependence on tMAC in spermatocytes. Integrative analysis of our data indicated that MMB/dREAM represses genes that are not expressed in spermatogenesis, whereas tMAC recruits Mip40 for subsequent gene activation in spermatocytes. Conclusions: Discovered interdependencies allow to formulate a renewed model for tMAC and tTAFs action in Drosophila spermatogenesis demonstrating how tissue-specific genes are regulated.

AB - Background: During Drosophila spermatogenesis, testis-specific meiotic arrest complex (tMAC) and testis-specific TBP-associated factors (tTAF) contribute to activation of hundreds of genes required for meiosis and spermiogenesis. Intriguingly, tMAC is paralogous to the broadly expressed complex Myb-MuvB (MMB)/dREAM and Mip40 protein is shared by both complexes. tMAC acts as a gene activator in spermatocytes, while MMB/dREAM was shown to repress gene activity in many cell types. Results: Our study addresses the intricate interplay between tMAC, tTAF, and MMB/dREAM during spermatogenesis. We used cell type-specific DamID to build the DNA-binding profiles of Cookie monster (tMAC), Cannonball (tTAF), and Mip40 (MMB/dREAM and tMAC) proteins in male germline cells. Incorporating the whole transcriptome analysis, we characterized the regulatory effects of these proteins and identified their gene targets. This analysis revealed that tTAFs complex is involved in activation of achi, vis, and topi meiosis arrest genes, implying that tTAFs may indirectly contribute to the regulation of Achi, Vis, and Topi targets. To understand the relationship between tMAC and MMB/dREAM, we performed Mip40 DamID in tTAF- and tMAC-deficient mutants demonstrating meiosis arrest phenotype. DamID profiles of Mip40 were highly dynamic across the stages of spermatogenesis and demonstrated a strong dependence on tMAC in spermatocytes. Integrative analysis of our data indicated that MMB/dREAM represses genes that are not expressed in spermatogenesis, whereas tMAC recruits Mip40 for subsequent gene activation in spermatocytes. Conclusions: Discovered interdependencies allow to formulate a renewed model for tMAC and tTAFs action in Drosophila spermatogenesis demonstrating how tissue-specific genes are regulated.

KW - DamID

KW - Drosophila

KW - Gene regulation

KW - Spermatogenesis

KW - Gene Expression Profiling/methods

KW - Drosophila Proteins/genetics

KW - Transcriptional Activation

KW - Gene Expression Regulation

KW - Cell Cycle Proteins/metabolism

KW - Male

KW - Meiosis

KW - Gene Regulatory Networks

KW - Organ Specificity

KW - DNA-Binding Proteins/metabolism

KW - Drosophila/genetics

KW - Animals

KW - Transcription Factors/metabolism

KW - Carrier Proteins/genetics

KW - Testis/chemistry

KW - Nuclear Proteins/metabolism

KW - ACTIVATION

KW - RNA

KW - PROMOTERS

KW - CELLS

KW - TRANSCRIPTION

KW - DIFFERENTIATION

KW - PROTEINS

KW - EXPRESSION

KW - MELANOGASTER

KW - MYB-MUVB/DREAM COMPLEX

UR - http://www.scopus.com/inward/record.url?scp=85044712235&partnerID=8YFLogxK

U2 - 10.1186/s13072-018-0183-3

DO - 10.1186/s13072-018-0183-3

M3 - Article

C2 - 29609617

AN - SCOPUS:85044712235

VL - 11

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

SN - 1756-8935

IS - 1

M1 - 14

ER -