scholarly journals Super-Enhancers Dysregulations in Hematological Malignancies

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 196
Author(s):  
Yannis Belloucif ◽  
Camille Lobry
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Regulatory Elements ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Cancer Types ◽  
Acute Myeloid

Hematological malignancies affecting either the lymphoid or the myeloid lineages involve epigenetic mutations or dysregulation in the majority of cases. These epigenetic abnormalities can affect regulatory elements in the genome and, particularly, enhancers. Recently, large regulatory elements known as super-enhancers, initially identified for their critical roles in cell-type specific expression regulation of genes controlling cell identity, have been shown to also be involved in tumorigenesis in many cancer types and hematological malignancies via the regulation of numerous oncogenes, including MYC. In this review, we highlight the existing links between super-enhancers and hematological malignancies, with a particular focus on acute myeloid leukemia, a clonal hematopoietic neoplasm with dismal outcomes, resulting in an uncontrolled proliferation of myeloblasts, abnormally blocked during differentiation and accumulating within the patient’s bone marrow. We report recent works, performed during the last few years, treating this subject and consider the possibility of targeting oncogenic regulatory elements, as well as the effectiveness and limitations reported so far for such strategies.

Viral Strategies for Targeting the Central and Peripheral Nervous Systems

2018 ◽  
Vol 41 (1) ◽  
pp. 323-348 ◽  
Author(s):  
Claire N. Bedbrook ◽  
Benjamin E. Deverman ◽  
Viviana Gradinaru
Keyword(s):  
Nervous System ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Recombinant Viruses ◽  
Neuronal Populations ◽  
Neuroscience Research ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type–specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.

scholarly journals Positive and negative elements regulate a melanocyte-specific promoter

1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding
Keyword(s):  
Protein Interactions ◽  
Regulatory Element ◽  
Basal Layer ◽  
Regulatory Elements ◽  
Hair Follicles ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.

scholarly journals Positive and negative elements regulate a melanocyte-specific promoter.

1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662 ◽  
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding
Keyword(s):  
Protein Interactions ◽  
Regulatory Element ◽  
Basal Layer ◽  
Regulatory Elements ◽  
Hair Follicles ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.

Regulation of the PU.1 gene by distal elements

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2958-2965 ◽  
Author(s):  
Youlin Li ◽  
Yutaka Okuno ◽  
Pu Zhang ◽  
Hanna S. Radomska ◽  
Hui-min Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Transcriptional Start Site ◽  
Critical Role ◽  
Myeloid Cell ◽  
Regulatory Elements ◽  
Cell Type ◽  
Specific Expression ◽  
Deoxyribonuclease I ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Abstract The transcription factor PU.1 (also known as Spi-1) plays a critical role in the development of the myeloid lineages, and myeloid cells derived from PU.1−/− animals are blocked at the earliest stage of myeloid differentiation. Expression of the PU.1 gene is tightly regulated during normal hematopoietic development, and dysregulation of PU.1 expression can lead to erythroleukemia. However, relatively little is known about how the PU.1 gene is regulated in vivo. Here it is shown that myeloid cell type–specific expression of PU.1 in stable cell lines and transgenic animals is conferred by a 91-kilobase (kb) murine genomic DNA fragment that consists of the entire PU.1 gene (20 kb) plus approximately 35 kb of upstream and downstream sequences, respectively. To further map the important transcriptional regulatory elements, deoxyribonuclease I hypersensitive site mapping studies revealed at least 3 clusters in the PU.1 gene. A 3.5-kb fragment containing one of these deoxyribonuclease I hypersensitive sites, located −14 kb 5′ of the transcriptional start site, conferred myeloid cell type–specific expression in stably transfected cell lines, suggesting that within this region is an element important for myeloid specific expression of PU.1. Further analysis of this myeloid-specific regulatory element will provide insight into the regulation of this key transcriptional regulator and may be useful as a tool for targeting expression to the myeloid lineage.

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific
Sign in / Sign up

Export Citation Format

Share Document