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Basic helix-loop-helix transcription factors MYC-MAX and CLOCK-BMAL1 associate with histones for E-box access

ABSTRACT: Basic helix-loop-helix transcription factors MYC-MAX and CLOCK-BMAL1 associate with histones for E-box access

PROVIDER: PRJNA931927 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23347369_1.fastq.gz	Fastqsanger.gz
	SRR23347369_2.fastq.gz	Fastqsanger.gz
	SRR23347370_1.fastq.gz	Fastqsanger.gz
	SRR23347370_2.fastq.gz	Fastqsanger.gz
	SRR23347371_1.fastq.gz	Fastqsanger.gz

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Basic helix-loop-helix transcription factors MYC-MAX and CLOCK-BMAL1 associate with histones for E-box access

Project description:Basic helix-loop-helix (bHLH) transcription factors (TF) recognize E-boxes (CANNTG) and include over 100 members. Here we investigated how chromatinised E-boxes are engaged by two structurally diverse bHLH family members; the proto-oncogene MYC-MAX and the circadian TF, CLOCK-BMAL1. Both bind E-boxes preferentially near the nucleosomal entry/exit sites. Structural studies with artificial or endogenous nucleosome sequences illustrate that MYC-MAX/CLOCK-BMAL1 trigger DNA release from histones to gain access. The CLOCK-BMAL1 PAS dimerization domains engage the histone-octamer disc atop the H2A/H2B acidic patch, an interaction critical for circadian cycling. Binding of tandem E-boxes at endogenous DNA sequences is similarly achieved through direct interactions between two CLOCK-BMAL1 protomers and histones. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B/H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerisation domain jointly determine the histone contact, the affinity, and the degree of competition/cooperativity with other nucleosome-bound factors.

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Basic helix-loop-helix transcription factor Tcf21 is downstream target of male sex-determining gene SRY

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Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED

Project description:Neuroendocrine (NE) cells use large dense core vesicles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secretory pathway. The DIMM basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two independent genome-wide analyses of DIMM’s activities: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to characterize their transcriptional profile. By this combined approach, we showed that DIMM binds to conserved E-boxes in enhancers of 212 genes whose expression is enriched in DIMM-expressing NE cells. DIMM binds preferentially to certain E-boxes within first introns of specific gene isoforms. Statistical machine learning revealed that flanking regions of putative DIMM binding sites contribute to its DNA binding specificity. DIMM’s transcriptional repertoire features at least 20 LDCV constituents. In addition, DIMM notably targets the pro-secretory transcription factor, CREB-A, but significantly, DIMM does not target any neuropeptide genes. DIMM therefore prescribes the scale of secretory activity in NE neurons, by a systematic control of the regulated secretory pathway at steps that are both proximal and distal.

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Basic helix-loop-helix transcription factor Tcf21 is downstream target of male sex-determining gene SRY

Project description:The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development. We used microarrays to determine genes whose expression was stimulated in rat E13 ovarian cell sub-cultures in the presence of a pCMV-myc-expression plasmid over-expressing the Sry, Tsf21, and/or Tcf12 (Reb-alfa) genes. RNA samples from the control group (untreated E13 rat ovarian cells) are compared to RNA from 4 groups of treated E13 rat ovarian cells: 1) Sry overexpressing, 2) Tcf21 overexpressing, 3) Tcf12 (Reb alfa) overexpressing, and 4) Tcf21 + Tcf12 (Reb-alfa) overexpressing. Untreated E13 testis cell sub-cultures were also analyzed. 3 biological replicates each group.

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Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED

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