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13. Structural insights into the recognition of the A/T‐rich motif in target gene promoters by the LMX1a homeobox domain.

Author

Lin, Liqing, Deng, Jie, Peng, Junhui, Cui, Jing, Wang, Lei, Zhang, Min, Gao, Jia, Li, Fudong, Shi, Yunyu, and Lv, Mengqi

Subjects
*TRANSCRIPTION factors, *HOMEOBOX genes, *NEURON development, *GENETIC transcription, *RECOGNITION (Psychology), *CELL differentiation
Abstract

LIM homeodomain transcription factor 1‐alpha (LMX1a) is a neuronal lineage‐specific transcription activator that plays an essential role during the development of midbrain dopaminergic (mDA) neurons. LMX1a induces the expression of multiple key genes, which ultimately determine the morphology, physiology, and functional identity of mDA neurons. This function of LMX1a is dependent on its homeobox domain. Here, we determined the structures of the LMX1a homeobox domain in complex with the promoter sequences of the Wnt family member 1 (WNT1) or paired like homeodomain 3 (Pitx3) gene, respectively. The complex structures revealed that the LMX1a homeobox domain employed its α3 helix and an N‐terminal loop to achieve specific target recognition. The N‐terminal loop (loop1) interacted with the minor groove of the double‐stranded DNA (dsDNA), whereas the third α‐helix (α3) was tightly packed into the major groove of the dsDNA. Structure‐based mutations in the α3 helix of the homeobox domain significantly reduced the binding affinity of LMX1a to dsDNA. Moreover, we identified a nonsyndromic hearing loss (NSHL)‐related mutation, R199, which yielded a more flexible loop and disturbed the recognition in the minor groove of dsDNA, consistent with the molecular dynamics (MD) simulations. Furthermore, overexpression of Lmx1a promoted the differentiation of SH‐SY5Y cells and upregulated the transcription of WNT1 and PITX3 genes. Hence, our work provides a detailed elucidation of the specific recognition between the LMX1a homeobox domain and its specific dsDNA targets, which represents valuable information for future investigations of the functional pathways that are controlled by LMX1a during mDA neuron development. [ABSTRACT FROM AUTHOR]

Published
2024
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34. KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition

Author

Boila, Liberalis Debraj, primary, Ghosh, Subhadeep, additional, Bandyopadhyay, Subham, additional, Lin, Liqing, additional, Murison, Alexander, additional, Zeng, Andy, additional, Shaikh, Wasim, additional, Bhowmik, Satyaki, additional, Muddineni, Siva Sai Naga Anurag, additional, Biswas, Mayukh, additional, Sinha, Sayantani, additional, Chatterjee, Shankha Subhra, additional, Mbong, Nathan, additional, Gan, Olga, additional, Bose, Anwesha, additional, Chakraborty, Sayan, additional, Arruda, Andrea, additional, Kennedy, James, additional, Mitchell, Amanda, additional, Lechman, Eric, additional, Banerjee, Debasis, additional, Milyavsky, Michael, additional, Minden, Mark, additional, Dick, John, additional, and Sengupta, Amitava, additional

Published
2022
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45. The Role of Obstetric Factors, miRNA-30d and miRNA-181a in Postpartum Women with Pelvic Organ Prolapse

Author

Lin,Wenyu, Lin,Liqing, Dong,Binhua, Chen,Lihua, Lei,Huifang, Gao,Yuqin, Chen,Yaojia, and Sun,Pengming

Subjects
Risk Management and Healthcare Policy
Abstract

Wenyu Lin,1,2,* Liqing Lin,3,* Binhua Dong,2,4 Lihua Chen,1 Huifang Lei,1,2 Yuqin Gao,1,2 Yaojia Chen,1,2 Pengming Sun1,2,4 1Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3Department of Women’s Health Care, Quanzhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 4Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengming SunDirector of Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail sunfemy@hotmail.comBackground: The diagnosis of postpartum pelvic organ prolapse (POP) relies on symptoms combined with pelvic organ prolapse-quantification (POP-Q) and lacks serological indicators. The objective of this study was to assess serum elastin, type I collagen, miRNA-30d, and miRNA-181a in the early postpartum period to identify hematologic predictors of POP.Material and Methods: The study included 1013 42- to 60-day-postpartum women who had delivered at Quanzhou Women’s and Children’s Hospital from October 1, 2016, to October 31, 2017. This study was performed in accordance with the Declaration of Helsinki. The pregnancy and childbirth characteristics and pelvic floor function were evaluated. Forty cases with and without POP were matched, and serum elastin and type I collagen were determined by enzyme-linked immunosorbent assay (ELISA). Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miRNA-30d and miRNA-181a in 15 pairs.Results: Of the 1013 women recruited, 699 (69.00%) were diagnosed with POP. The mean age was 29.00 years old, and the mean body mass index (BMI) was 22.6 kg/m2. In the univariate analysis, age ≥ 35 years (OR, 1.449; 95% CI, 0.965, 2.298), postpartum BMI ≥ 24 (OR, 4.402; 95% CI, 2.657, 6.148), neonatal weight ≥ 4 kg (OR, 4.832; 95% CI, 1.373, 17.290) and vaginal delivery (OR, 2.751; 95% CI, 1.855, 4.081) were risk factors for postpartum POP. There were no significant differences in the concentrations of serum elastin and type I collagen between the groups (P=0.52; P=0.26). There were significant differences in the concentrations of miRNA-30d and miRNA-181a between the groups (P=0.004; P=0.003).Conclusion: miRNA-30d and miRNA-181a tended to be increased in women with POP and could be potential clinical predictors.Keywords: elastin, miRNA-30d, miRNA-181a, pelvic organ prolapse, type I collagen

Published
2020

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